564 results on '"Tumor-Derived"'
Search Results
2. Development and Clinical Application of Tumor-derived Exosomes in Patients with Cancer
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Neda Ketabchi, Iman Seyhoun, Maria Kavianpour, Mahshid Saleh, Somayeh Ebrahimi-Barough, Negar Noorbakhsh, and Javad Verdi
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Carcinogenesis ,business.industry ,Medicine (miscellaneous) ,Cancer ,General Medicine ,Tumor-Derived ,Exosomes ,medicine.disease_cause ,medicine.disease ,Microvesicles ,Metastasis ,MicroRNAs ,Immune system ,Neoplasms ,microRNA ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Cancer research ,Humans ,Cancer vaccine ,business - Abstract
A tumor is an abnormal growth of cells within a tissue that can lead to death due to late diagnosis, poor prognosis, drug resistance, and finally enhanced metastasis formation. Exosomes are nanovesicles that have been derived from all the different cell types. These vesicles can transfer various molecules, including the distinct form of nucleic acids (mRNA, miRNA, and circRNA) and proteins. Tumor-derived exosomes (TEXs) have exceptionally important roles through multiple molecular and cellular pathways like progression, tumorigenesis, drug resistance, and as well as metastasis. TEXs are detectable in all body fluids such as serum and urine, a convenient and non-invasive way to access these nano-sized vesicles. TEXs lead to the symptom expression of genetic aberrations in the tumor cell population, making them an accurate and sensitive biomarker for the diagnosis and prognosis of tumors. On the other hand, TEXs contain major histocompatibility complexes (MHCs) and play important dual roles in regulating tumor immune responses: they can mediate both immune activation and suppression through tumor-associated immunity. Despite numerous scientific studies, there are still many technical barriers to distinguish TEXs from non-tumor-derived exosomes. Even so, removing exosomes leading to a wide difference in outcomes inside a patient's body. Hence, controversial pieces of evidence have demonstrated the vital role of TEXs as hopeful biomarkers for the early detection of cancers, evaluation of therapeutic effects, and monitoring of the patient.
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- 2022
3. A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy
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Isrha Taha, Jose Javier Bravo-Cordero, Chandrani Mondal, Ana Rita Nobre, Julie Di Martino, Alexandra Naba, Elana J. Fertig, Julio A. Aguirre-Ghiso, and Eduardo F. Farias
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Type III collagen ,Cancer Research ,Text mining ,Oncology ,business.industry ,Niche ,Dormancy ,Tumor cells ,Biology ,Tumor-Derived ,business ,Cell biology ,Uncategorized - Abstract
Cancer cells disseminate from primary tumors and seed in distant organs, where they can remain dormant for many years before forming clinically detectable metastases. Little is known about how extracellular matrix (ECM) sensing and remodeling can induce and sustain dormancy of disseminated tumor cells (DTCs). Another unanswered question is whether dormant cells themselves are able to assemble ECM niches to sustain their phenotype. From an analysis of the ECM proteome, we found that dormant cancer cells assemble an ECM niche enriched in type III collagen. Tumor-derived, but not stroma-derived type III collagen is required to sustain tumor dormancy as its disruption restores proliferation of dormant cancer cells. Mechanistically, we show that type III collagen interacts with DDR1 to activate STAT1 signaling to induce and maintain dormancy. Second harmonic generation two-photon microscopy further reveals that the dormancy-to-reactivation transition is accompanied by changes in collagen three-dimensional architecture and type III collagen abundance. In vivo, exogenous type III collagen stops tumor growth by inducing dormancy and prevents reawakening of residual dormant cells by prolonging their quiescence. Analysis of clinical samples reveals that type III collagen levels are increased in tumors from head and neck squamous cell carcinoma (HNSCC) lymph node negative patients when compared lymph node positive patients. Our data reveal a novel mechanism by which dormant DTCs depend on the assembly of a type III collagen-rich ECM niche to maintain quiescence. Manipulation of these mechanisms could serve as a self-sustained barrier to metastasis through DTCs dormancy induction.
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- 2023
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4. Corrigendum to 'Heparan sulfate analogues regulate tumor-derived exosome formation that attenuates exosome functions in tumor processes' [Int. J. Biol. Macromol. 187 (2021) 481–491]
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Danhui Wang, Min Zhu, Yan Zhang, Jinghua Chen, Chao Deng, Mingzhu Kang, Xiaotao Wu, Yiwei Hu, and Liping Teng
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chemistry.chemical_compound ,chemistry ,Structural Biology ,INT ,General Medicine ,Heparan sulfate ,Tumor-Derived ,Molecular Biology ,Biochemistry ,Exosome ,Cell biology - Published
- 2021
5. TLR ligand loaded exosome mediated immunotherapy of established mammary Tumor in mice
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Pelin Gülizar Ersan, Muzaffer Yildirim, Tugce Bildik, Unal Metin Tokat, Ihsan Gursel, Nilsu Turay, Tugce Yildirim, Ozgur Sahin, Bilgehan Ibibik, Irem Evcili, Yıldırım, Muzaffer, Yıldırım, Tuğçe Canavar, Turay, Nilsu, Bildik, Tuğçe, İbibik, Bilgehan, Evcili, İrem, Ersan, Pelin Gülizar, Tokat, Ünal M., and Gürsel, İhsan
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CpG Oligodeoxynucleotide ,medicine.medical_treatment ,Immunology ,Breast tumor ,Breast Neoplasms ,Exosomes ,Cancer Vaccines ,Exosome ,Memory T Cells ,Mice ,Immune system ,Adjuvants, Immunologic ,Antigens, Neoplasm ,TLR ,Cell Line, Tumor ,Cancer vaccine ,medicine ,Animals ,Humans ,Immunology and Allergy ,Immune response ,Chemistry ,Immunogenicity ,Immunotherapy ,Th1 Cells ,Tumor-Derived ,Tumor antigen ,Toll-Like Receptor 3 ,Disease Models, Animal ,Poly I-C ,Oligodeoxyribonucleotides ,Toll-Like Receptor 9 ,Cancer research ,Female - Abstract
Tumor-derived exosomes (TEXs) could be harnessed as an immunotherapeutic cancer vaccine. These nanovesicles are inherently possesses rich tumor antigen reservoirs. Due to their undesirable features such as poor or limited immunogenicity as well as facilitation of cancer development via mediating communication between tumor cells TEXs could be transformed into an effective immune adjuvant delivery system that initiates a strong humoral and cell-mediated tumor-specific immune response. Engineering TEXs to harbor immunostimulatory molecules still remains a challenge. Previously, we demonstrated that nucleic acid ligand encapsulated liposomes could trigger synergistic strong humoral, and cell mediated immune responses and provokes tumor regression to that of their standalone counterparts. In this study, we evaluated to immunogenicity of 4T1/Her2 cell-derived exosomes upon loading them with two potent immuno adjuvant, a TLR9 ligand, K-type CpG ODN and a TLR3 ligand, p(I:C). Engineered TEXs co-encapsulating both ligands displayed boosted immunostimulatory properties by activating antigen-specific primary and memory T cell responses. Furthermore, our exosome-based vaccine candidate elicited robust Th1-biased immunity as evidenced by elevated secretion of IgG2a and IFNγ. In a therapeutic cancer model, administration of4T1 tumor derived exosomes loaded with CpG ODN and p(I:C) to animals regress tumor growth in 4T1 tumor-bearing mice. Taken together this work implicated that an exosome-based therapeutic vaccine promoted strong cellular and humoral anti-tumor immunity that is sufficient to reverse established tumors. This approach offers a personalized tumor therapy strategy that could be implemented in the clinic.
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- 2021
6. Tumor-Derived Cell Culture Model for the Investigation of Meningioma Biology
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Erik N. Uhlmann, Rafael A Vega, Matthew P. Anderson, Hemant Varma, Martina Stippler, Justin M. Moore, Ron L. Alterman, Rosalia Rabinovsky, Rachid El Fatimy, Anna M. Krichevsky, Ajith J. Thomas, Franciela C Kipper, Ekkehard M. Kasper, and Erik J. Uhlmann
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Pathology ,medicine.medical_specialty ,Central nervous system ,Cell Culture Techniques ,AcademicSubjects/MED00994 ,Tumor cells ,Biology ,Pathology and Forensic Medicine ,Meningioma ,Cellular and Molecular Neuroscience ,Tissue culture ,Cultured human meningioma tumor-derived cells ,Meningeal Neoplasms ,Tumor Cells, Cultured ,medicine ,Humans ,Meningioma model ,Fetus ,Medical treatment ,General Medicine ,Original Articles ,Tumor-Derived ,medicine.disease ,nervous system diseases ,medicine.anatomical_structure ,Neurology ,Neurology (clinical) ,Cell culture model - Abstract
Meningioma is the most common primary central nervous system tumor. Although mostly nonmalignant, meningioma can cause serious complications by mass effect and vasogenic edema. While surgery and radiation improve outcomes, not all cases can be treated due to eloquent location. Presently no medical treatment is available to slow meningioma growth owing to incomplete understanding of the underlying pathology, which in turn is due to the lack of high-fidelity tissue culture and animal models. We propose a simple and rapid method for the establishment of meningioma tumor-derived primary cultures. These cells can be maintained in culture for a limited time in serum-free media as spheres and form adherent cultures in the presence of 4% fetal calf serum. Many of the tissue samples show expression of the lineage marker PDG2S, which is typically retained in matched cultured cells, suggesting the presence of cells of arachnoid origin. Furthermore, nonarachnoid cells including vascular endothelial cells are also present in the cultures in addition to arachnoid cells, potentially providing a more accurate tumor cell microenvironment, and thus making the model more relevant for meningioma research and high-throughput drug screening.
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- 2021
7. Multi‐miRNA panel of tumor‐derived extracellular vesicles as promising diagnostic biomarkers of early‐stage breast cancer
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Hyo Jung Lee, Sunyoung Park, Hogyeong Gwak, Minwoo Kim, Jee Ye Kim, Kyung A. Hyun, Hyo Il Jung, and Seung Il Kim
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Genetics, Genomics and Proteomics ,Cancer Research ,Breast Neoplasms ,Integrin alpha6 ,Extracellular vesicles ,early‐stage breast cancer ,Extracellular Vesicles ,Breast cancer ,Cell Line, Tumor ,Databases, Genetic ,microRNA ,Biomarkers, Tumor ,Humans ,Diagnostic biomarker ,Medicine ,Liquid biopsy ,Stage (cooking) ,Early Detection of Cancer ,Neoplasm Staging ,liquid biopsy ,business.industry ,Gene Expression Profiling ,Original Articles ,General Medicine ,Microfluidic Analytical Techniques ,Tumor-Derived ,Epithelial Cell Adhesion Molecule ,medicine.disease ,Up-Regulation ,Biomarker (cell) ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Oncology ,Case-Control Studies ,MCF-7 Cells ,Cancer research ,biomarker ,Original Article ,Female ,business - Abstract
Extracellular vesicles (EV) have been emerging as potential biomarkers for disease monitoring. In particular, tumor‐derived EV (TDE) are known to carry oncogenic miRNA, so they can be used for diagnosis of early cancer by analyzing the expression levels of EV‐miRNA circulating in the blood. Here, using our novel microfluidic device, we rapidly and selectively isolate cancerous EV expressing breast cancer‐derived surface markers CD49f and EpCAM within 2 minutes. Based on seven candidates of miRNA nominated from The Cancer Genome Atlas (TCGA) database, the expression levels of miRNA in TDE were validated in a total of 82 individuals, including 62 breast cancer patients and 20 healthy controls. Among seven candidates, four miRNAs (miR‐9, miR‐16, miR‐21, and miR‐429) from the EV were highly elevated in early‐stage breast cancer patients compared with healthy donors. The combination of significant miRNAs from specific EV has high sensitivities of 0.90, 0.86, 0.88, and 0.84 of the area under the receiver operating characteristic curve (AUC) in each subtype (luminal A, luminal B, HER‐2, and triple‐negative) of early‐stage breast cancer. Our results suggest that the combination of four miRNA signatures of specific EV could serve as a sensitive and specific biomarker and enable early diagnosis of breast cancer using liquid biopsy., A new combination of miRNA from cancer‐specific extracellular vesicles was proposed for the highly sensitive and specific diagnosis of early‐stage breast cancer in association with a microfluidic‐based immuno‐isolation technique. These findings suggest that miRNA in EV could be used as important biomarkers for the early detection of breast cancer and identification of cancer subtype.
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- 2021
8. Surface enhanced Raman spectroscopy‐based immunoassay detection of tumor‐derived extracellular vesicles to differentiate pancreatic cancers from chronic pancreatitis
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Nariman Banaei, Byung Kim, and Javad Moshfegh
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medicine.diagnostic_test ,Chemistry ,Tumor-Derived ,Surface-enhanced Raman spectroscopy ,medicine.disease ,Extracellular vesicles ,Molecular biology ,symbols.namesake ,Immunoassay ,Pancreatic cancer ,symbols ,medicine ,Pancreatitis ,General Materials Science ,Raman spectroscopy ,Spectroscopy - Published
- 2021
9. Tumor-Derived Extracellular Vesicles: Their Role in Immune Cells and Immunotherapy
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Ting Huyan, Xiaojie Zhou, Qi Li, Jinzhao Chen, Kab Ibrahim Salma, Feiyu Han, Suna Cai, and Mengjiao Li
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medicine.medical_treatment ,Biophysics ,Pharmaceutical Science ,Bioengineering ,Review ,Cell Communication ,Biology ,Metastasis ,Biomaterials ,Extracellular Vesicles ,Immune system ,Neoplasms ,Drug Discovery ,medicine ,Humans ,Cytotoxicity ,Vesicle ,Organic Chemistry ,Biological Transport ,General Medicine ,Immunotherapy ,Tumor-Derived ,regulatory effects ,medicine.disease ,Cell biology ,drug delivery ,Drug delivery ,immune cell ,tumor-derived extracellular vesicles ,Intracellular - Abstract
Nowadays, tumor has been the serious threat to human health and life. To further explore the mechanism of tumor genesis and development is necessarily for developing the effective treatment strategy. Extracellular vesicles are the vesicles secreted by almost all types of cells, and they play an important part in intercellular communication by transporting their cargoes. Immune cells are the vital components of the human defense system, which defense against infection and tumor through cytotoxicity, immune surveillance, and clearance. However, via release tumor-derived extracellular vesicles, tumor could induce immune cells dysfunction to facilitate its proliferation and metastasis. Studies have shown that tumor-derived extracellular vesicles play dual role on immune cells by their specific cargoes. Here, we reviewed the effects of tumor-derived extracellular vesicles on immune cells in recent years and also summarized their research progress in the tumor immunotherapy and diagnosis.
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- 2021
10. The roles of tumor-derived exosomes in altered differentiation, maturation and function of dendritic cells
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Leila Asef-Kabiri, Hassan Yousefi, Hamzeh Sarvnaz, Nahid Eskandari, Majid Salehi, Reza Hosseini, and Mohammad Esmaeil Akbari
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0301 basic medicine ,Cancer Research ,Priming (immunology) ,Context (language use) ,Review ,Biology ,Exosomes ,Exosome ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neoplasms ,Tumor Microenvironment ,Animals ,Humans ,RC254-282 ,Tumor ,Immunity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell Differentiation ,Dendritic cell ,Dendritic Cells ,Tumor-Derived ,Microvesicles ,Cell biology ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Tumor Escape ,Function (biology) - Abstract
Tumor-derived exosomes (TDEs) have been shown to impede anti-tumor immune responses via their immunosuppressive cargo. Since dendritic cells (DCs) are the key mediators of priming and maintenance of T cell-mediated responses; thus it is logical that the exosomes released by tumor cells can exert a dominant influence on DCs biology. This paper intends to provide a mechanistic insight into the TDEs-mediated DCs abnormalities in the tumor context. More importantly, we discuss extensively how tumor exosomes induce subversion of DCs differentiation, maturation and function in separate sections. We also briefly describe the importance of TDEs at therapeutic level to help guide future treatment options, in particular DC-based vaccination strategy, and review advances in the design and discovery of exosome inhibitors. Understanding the exosomal content and the pathways by which TDEs are responsible for immune evasion may help to revise treatment rationales and devise novel therapeutic approaches to overcome the hurdles in cancer treatment.
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- 2021
11. P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas
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Shauli Talmor, Ignacio Mastandrea, Tova Waks, Zelig Eshhar, Liat Rousso-Noori, Dinorah Friedmann-Morvinski, Tambet Teesalu, Maarja Haugas, Luis Álvarez-Vallina, and Anat Levin
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0301 basic medicine ,Male ,medicine.medical_treatment ,T-Lymphocytes ,General Physics and Astronomy ,Angiogenesis Inhibitors ,Cancer immunotherapy ,Immunotherapy, Adoptive ,Mice ,0302 clinical medicine ,Receptor ,Multidisciplinary ,Receptors, Chimeric Antigen ,Brain Neoplasms ,Serine Endopeptidases ,Glioma ,Tumor-Derived ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,T cell ,Science ,Receptors, Antigen, T-Cell ,Mice, Nude ,Antineoplastic Agents ,General Biochemistry, Genetics and Molecular Biology ,Article ,Mitochondrial Proteins ,03 medical and health sciences ,Antigen ,Antigens, Neoplasm ,Cell Line, Tumor ,medicine ,Animals ,Humans ,neoplasms ,Aged ,business.industry ,General Chemistry ,Immunotherapy ,medicine.disease ,Xenograft Model Antitumor Assays ,Chimeric antigen receptor ,nervous system diseases ,Mice, Inbred C57BL ,CNS cancer ,body regions ,030104 developmental biology ,Cell culture ,Cancer research ,business ,Carrier Proteins ,Glioblastoma - Abstract
Glioblastoma is considered one of the most aggressive malignancies in adult and pediatric patients. Despite decades of research no curative treatment is available and it thus remains associated with a very dismal prognosis. Although recent pre-clinical and clinical studies have demonstrated the feasibility of chimeric antigen receptors (CAR) T cell immunotherapeutic approach in glioblastoma, tumor heterogeneity and antigen loss remain among one of the most important challenges to be addressed. In this study, we identify p32/gC1qR/HABP/C1qBP to be specifically expressed on the surface of glioma cells, making it a suitable tumor associated antigen for redirected CAR T cell therapy. We generate p32 CAR T cells and find them to recognize and specifically eliminate p32 expressing glioma cells and tumor derived endothelial cells in vitro and to control tumor growth in orthotopic syngeneic and xenograft mouse models. Thus, p32 CAR T cells may serve as a therapeutic option for glioblastoma patients., Chimeric antigen receptor (CAR) T cell therapy has been proposed as a promising approach for treating glioblastoma. Here the authors show that p32 is expressed in murine and human glioma and that p32-directed CAR-T cells promote anti-tumor responses in preclinical models by targeting glioma cells and tumor derived endothelial cells.
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- 2021
12. Tumor-derived exosomal components: the multifaceted roles and mechanisms in breast cancer metastasis
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Chongru Zhao, Yi Yi, Yichen Wang, Yiping Wu, Mingchen Xiong, Qi Zhang, Xiao Luo, Weijie Hu, Wenchang Lv, Yufang Tan, Dawei Wang, and Haiping Wang
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Cancer microenvironment ,Cancer Research ,Immunology ,Cancer metastasis ,Breast Neoplasms ,Review Article ,Biology ,Exosomes ,Malignancy ,Non-coding RNAs ,Metastasis ,Cellular and Molecular Neuroscience ,Breast cancer ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Humans ,Neoplasm Metastasis ,Tumor microenvironment ,QH573-671 ,Breast cancer metastasis ,Cell Biology ,Tumor-Derived ,medicine.disease ,Microvesicles ,Cancer research ,Female ,Cytology - Abstract
Breast cancer (BC) is the most frequently invasive malignancy and the leading cause of tumor-related mortality among women worldwide. Cancer metastasis is a complex, multistage process, which eventually causes tumor cells to colonize and grow at the metastatic site. Distant organ metastases are the major obstacles to the management of advanced BC patients. Notably, exosomes are defined as specialized membrane-enclosed extracellular vesicles with specific biomarkers, which are found in a wide variety of body fluids. Recent studies have demonstrated that exosomes are essential mediators in shaping the tumor microenvironment and BC metastasis. The transferred tumor-derived exosomes modify the capability of invasive behavior and organ-specific metastasis in recipient cells. BC exosomal components, mainly including noncoding RNAs (ncRNAs), proteins, lipids, are the most investigated components in BC metastasis. In this review, we have emphasized the multifaceted roles and mechanisms of tumor-derived exosomes in BC metastasis based on these important components. The underlying mechanisms mainly include the invasion behavior change, tumor vascularization, the disruption of the vascular barrier, and the colonization of the targeted organ. Understanding the significance of tumor-derived exosomal components in BC metastasis is critical for yielding novel routes of BC intervention.
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- 2021
13. Tumor-derived exosomes: Nanovesicles made by cancer cells to promote cancer metastasis
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Duxin Sun, Hongwei Chen, Hongxiang Hu, and Venkata Chengalvala
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Therapeutic implications ,Exosome targeting ,RM1-950 ,Review ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Medicine ,Tumor-derived exosomes ,General Pharmacology, Toxicology and Pharmaceutics ,030304 developmental biology ,0303 health sciences ,business.industry ,Pre-metastatic niche ,Intravasation ,Cancer ,Tumor-Derived ,Vasculature leaky ,medicine.disease ,Extravasation ,Microvesicles ,030220 oncology & carcinogenesis ,Cancer cell ,Nanocarrier ,Cancer research ,Therapeutics. Pharmacology ,business ,Immunosuppression - Abstract
Nanomedicine usually refers to nanoparticles that deliver the functional drugs and siRNAs to treat cancer. Recent research has suggested that cancer cells can also make nanoparticles that also deliver functional molecules in promoting cancer metastasis, which is the leading cause of various cancer mortalities. This nanoparticle is called tumor-derived vesicles, or better-known as tumor-derived exosomes (TEXs). TEXs are nanoscale membrane vesicles (30–140 nm) that are released continuously by various types of cancer cells and contain tumor-derived functional biomolecules, including lipids, proteins, and genetic molecules. These endogenous TEXs can interact with host immune cells and epithelial cells locally and systemically. More importantly, they can reprogram the recipient cells in favor of promoting metastasis through facilitating tumor cell local invasion, intravasation, immune evasion, extravasation, and survival and growth in distant organs. Growing evidence suggests that TEXs play a key role in cancer metastasis. Here, we will review the most recent findings of how cancer cells harness TEXs to promote cancer metastasis through modulating vascular permeability, suppressing systemic immune surveillance, and creating metastatic niches. We will also summarize recent research in targeting TEXs to treat cancer metastasis., Graphical abstract We reviewed recent progress on understanding how tumor-derived exosomes (TEXs) promote metastasis through facilitating tumor cell local invasion, intravasation, immune evasion, extravasation, and growth in distant organs.Image 1
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- 2021
14. Systemic immunity upon local oncolytic virotherapy armed with immunostimulatory genes may be supported by tumor-derived exosomes
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Jessica Wenthe, Emma Eriksson, Sedigheh Naseri, Angelica Loskog, and Alireza Labani-Motlagh
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0301 basic medicine ,Oncolytic adenovirus ,Cancer Research ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,exosomes ,Major histocompatibility complex ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,CD40L ,4-1BBL ,Pharmacology (medical) ,dendritic cells ,biology ,Immunology in the medical area ,Dendritic cell ,Immunotherapy ,Tumor-Derived ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Microvesicles ,oncolytic adenovirus ,Oncolytic virus ,030104 developmental biology ,Oncology ,Immunologi inom det medicinska området ,030220 oncology & carcinogenesis ,LOAd703 ,biology.protein ,Cancer research ,Molecular Medicine ,Original Article ,costimulatory molecules - Abstract
Immunostimulatory gene therapy utilizing oncolytic viruses (OVs) as gene vehicles is a promising immunotherapy for cancer. Since viruses are immunogenic, systemic delivery can be troublesome due to neutralizing antibodies. Nevertheless, local delivery by intratumoral injection seems to induce systemic immune reactions. In this study, we demonstrate a novel mechanism of action of armed OV therapy suggesting that exosomes released by tumor cells infected with armed OV may participate to activate the immune system and this may also support systemic immunity. Tumor cell-derived exosomes commonly exert immunosuppressive functions. We hypothesized that exosomes derived from OV-infected tumor cells may instead be immunostimulatory. Human melanoma cells were infected by OVs armed with costimulatory molecules CD40 ligand (CD40L) and 4-1BB ligand (4-1BBL). Exosomes were purified and investigated for the presence of CD40L/4-1BBL mRNA and protein, and for their capacity to stimulate immune responses. The results show that the exosomes cargo transgenes. The exosomes from CD40L/4-1BBL-expressing tumor cells, or the viruses themselves, could stimulate robust dendritic cell (DC) activation with an enhanced level of major histocompatibility complex (MHC) and costimulatory molecules. Hence, exosomes after OV infection can locally activate immune responses at the tumor site and encounter immune cells such as DCs., Graphical Abstract, Tumor cells infected with armed oncolytic LOAd703 viruses release exosomes expressing two costimulatory transgenes CD40L and 4-1BBL, and such nanovesicles can activate dendritic cells in vitro. This behavior of tumor-derived exosomes is immunostimulatory rather than their immunosuppressive nature and can elicit antitumor immune responses.
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- 2021
15. Abstract PS4-36: Non-invasive evaluation of chemoresistance in breast cancers using circulating tumor associated cells
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S. Pawar, Rutuja Bhave, Raja Dhasarathan, Mahesh Ukade, Vineet Datta, Chirantan Bose, Harshal Bodke, Ajay Srinivasan, Stefan Schuster, Dadasaheb Akolkar, Shabista Khan, Cynthe Sims, Darshana Patil, Jatinder Bhatia, Vishakha Mhase, Sanket Patil, Rajan Datar, Sachin Apurwa, and Samruddhi Raut
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Cancer ,Immunotherapy ,Tumor-Derived ,medicine.disease ,Peripheral blood mononuclear cell ,Breast cancer ,Internal medicine ,Biopsy ,medicine ,Cytotoxic T cell ,business - Abstract
Background: Despite the development of Checkpoint Inhibitor Treatments (Immunotherapy) and Targeted anticancer agents, cytotoxic (chemotherapy) agents remain the mainstay of breast cancer treatments. However, treatment failure is often encountered in breast cancers owing to innate or acquired chemoresistance. Real time monitoring of inherent or incipient chemoresistance is an unmet need to minimize or prevent treatment failures and improve outcomes. However, prior efforts to determine chemoresistance have used tumor tissue or explants and are hence not suitable for repetitive monitoring. We present findings from a large cohort perspective observational study which shows that Circulating Tumor Associated Cells (CTACs) be isolated in sufficient numbers from peripheral blood and can be profiled in vitro for chemoresistance characteristics. Methods: 15 ml of peripheral blood was obtained from 1410 breast cancer patients, of whom 719 were treatment naïve and 691 had received prior systemic therapies. Matched tumor tissue was obtained by a biopsy (post-blood collection) in a subset of 68 cases. Peripheral blood mononuclear cells (PBMCs) were isolated from all blood samples and treated with an epigenetically activating treatment medium which exerts selective cytotoxicity towards non-malignant hematolymphoid cells and allows survival of apoptosis resistant malignant CTACs, which were defined as cells which were EpCAM+, PanCK+ and CD45+/-. Viable Tumor Derived Cells (TDCs) were harvested from biopsied tumor tissue (N=68). CTACs and TDCs were treated in vitro with cytotoxic chemotherapy agents that are used in Standard of Care (SoC) treatment protocols for breast cancer as single agents or in combinations. In 68 cases, concordance in Chemoresistance Profiles (CRP) was determined between CTACs and corresponding TDCs. In 681 pretreated cases, CRP of CTACs evaluated cumulative (innate and acquired) resistance following prior exposure to chemotherapy agents. In 685 therapy naïve cases, CRP of CTACs evaluated innate chemoresistance towards chemotherapy agents. Results: Among the 68 paired samples of CTACs and TDCs, there were 733 unique combinations of CTAC-TDC-drug, among which 366 pairs (50%) were concordant for chemo-resistance, 336 pairs (46%) were concordant for absence of resistance, and 31 pairs (4%) showed absence of concordance leading to a cumulative concordance of 96% in CRP between TDC and CTACs. Among the 681 pretreated cases, resistance towards ≥1 anticancer agents was observed in 67% of the samples. Among the 685 therapy naïve cases, resistance towards ≥1 anticancer agents was observed in 39% of the samples. Conclusion: The present study shows that sufficient CTACs can be harvested from peripheral blood for meaningful non-invasive chemoresistance profiling and that the resistance profiles of CTACs are concordant with that of tumor tissue. The present approach can identify innate as well as acquired chemoresistance and can guide selection of appropriate therapies. This approach can facilitate real time monitoring of chemoresistance and therapeutic course correction to minimize the risk of treatment failures. Citation Format: Darshana Patil, Dadasaheb Akolkar, Sanket Patil, Vishakha Mhase, Sachin Apurwa, Sushant Pawar, Rutuja Bhave, Mahesh Ukade, Samruddhi Raut, Harshal Bodke, Shabista Khan, Raja Dhasarathan, Vineet Datta, Stefan Schuster, Cynthe Sims, Jatinder Bhatia, Chirantan Bose, Ajay Srinivasan, Rajan Datar. Non-invasive evaluation of chemoresistance in breast cancers using circulating tumor associated cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-36.
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- 2021
16. Immunogenic Hybrid Nanovesicles of Liposomes and Tumor-Derived Nanovesicles for Cancer Immunochemotherapy
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Yulin Yu, Kun Tu, Qian Hu, Qi Qiao, Yi Wang, Jiao Zhang, Zhiping Zhang, Li Kong, Mei Hu, Xianya Qin, and Ting Yang
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medicine.medical_treatment ,General Physics and Astronomy ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Mice ,Drug Delivery Systems ,Immune system ,Cell Line, Tumor ,Neoplasms ,polycyclic compounds ,medicine ,Animals ,General Materials Science ,Doxorubicin ,Mice, Inbred BALB C ,Tumor microenvironment ,business.industry ,General Engineering ,Cancer ,Immunotherapy ,Tumor-Derived ,021001 nanoscience & nanotechnology ,medicine.disease ,0104 chemical sciences ,Liposomes ,Drug delivery ,Cancer research ,Immunogenic cell death ,0210 nano-technology ,business ,medicine.drug - Abstract
Exploring a rational delivery system of integrating chemotherapy with immunotherapy to broaden benefits of cancer immunochemotherapy is still under challenge. Herein, we developed doxorubicin (DOX)-loaded biomimetic hybrid nanovesicles (DOX@LINV) via fusing artificial liposomes (LIPs) with tumor-derived nanovesicles (TNVs) for combinational immunochemotherapy. DOX@LINV with a homologous targeting ability could deliver DOX to tumor tissue and elicit an effective immunogenic cell death response to improve the immunogenicity of a tumor. Meanwhile, the preserved tumor antigens and endogenous danger signals in DOX@LINV activated dendritic cells and induced a subsequent antigen-specific T cell immune response. DOX@LINV displayed a specific antitumor effect on murine melanoma, Lewis lung cancer, and 4T1 breast cancer based on the infiltration of effector immune cells and improvement of the immunosuppressive tumor microenvironment. Furthermore, the combination of DOX@LINV with immune checkpoint inhibitor amplified antitumor efficacy with 33.3% of the mice being tumor-free. Therefore, the hybrid LINV is a promising drug delivery platform with a boosted antitumor immune response for effective immunochemotherapy.
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- 2021
17. Identification of diverse tumor endothelial cell populations in malignant glioma
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Benjamin Deneen, Jeffrey C. Carlson, Chad J. Creighton, Brittney Lozzi, Alexander M. Herman, Emmet Huang-Hobbs, Williamson D Turner, Manuel Cantu Gutierrez, Burak Tepe, Joshua D. Wythe, Ganesh Rao, and Yiqun Zhang
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0301 basic medicine ,Cancer Research ,Endothelium ,Angiogenesis ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Glioma ,Tumor Microenvironment ,medicine ,Humans ,Tumor microenvironment ,Neovascularization, Pathologic ,Brain Neoplasms ,Endothelial Cells ,Tumor-Derived ,medicine.disease ,Lymphangiogenesis ,Editorial ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Tumor progression ,Cancer research ,Neurology (clinical) ,Carcinogenesis ,030217 neurology & neurosurgery - Abstract
BackgroundGlioblastoma is the most common and aggressive type of primary brain tumor, as most patients succumb to the disease less than two years after diagnosis. Critically, studies demonstrate that glioma recruits surrounding blood vessels, while some work suggests that tumor stem cells themselves directly differentiate into endothelial cells, yet the molecular and cellular dynamics of the endothelium in glioma are poorly characterized. The goal of this study was to establish molecular and morphological benchmarks for tumor associated vessels (TAVs) and tumor derived endothelial cells (TDECs) during glioblastoma progression.MethodsUsing In-Utero Electroporation and CRISPR/Cas9 genome engineering to generate a native, immunocompetent mouse model of glioma, we characterized vascular-tumor dynamics in three dimensions during tumor progression. We employed bulk and single-cell RNA-Sequencing to elucidate the relationship between TAVs and TDECs. We confirmed our findings in a patient derived orthotopic xenograft (PDOX) model.ResultsUsing a mouse model of glioma, we identified progressive alteration of vessel function and morphogenesis over time. We also showed in our mouse model that TDECs are a rare subpopulation that contributes to vessels within the tumor, albeit to a limited degree. Furthermore, transcriptional profiling demonstrates that both TAVs and TDECs are molecularly distinct, and both populations feature extensive molecular heterogeneity. Finally, the distinct molecular signatures of these heterogeneous populations are also present in human glioma.ConclusionsOur findings show extensive endothelial heterogeneity within the tumor and tumor microenvironment and provide insights into the diverse cellular and molecular mechanisms that drive glioma vascularization and angiogenesis during tumorigenesis.
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- 2020
18. Interactions between tumor-derived proteins and Toll-like receptors
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Ji Won Lee, Yeong-Min Park, Hee Dong Han, Sung Eun Lee, Young Seob Kim, Tae Heung Kang, Gun-Young Jang, and Kee-Jong Hong
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Cancer microenvironment ,0301 basic medicine ,Damp ,medicine.medical_treatment ,Clinical Biochemistry ,Inflammation ,Review Article ,Biology ,Biochemistry ,Immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neoplasms ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Alarmins ,Animals ,Humans ,Receptor ,Molecular Biology ,Tumor microenvironment ,Immune cell death ,Toll-Like Receptors ,Pattern recognition receptor ,food and beverages ,respiratory system ,Tumor-Derived ,Neoplasm Proteins ,Cell biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Cytokine ,Organ Specificity ,030220 oncology & carcinogenesis ,Molecular Medicine ,Disease Susceptibility ,medicine.symptom ,Protein Binding ,Signal Transduction - Abstract
Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment., Cancer: Boosting the right signals to suppress tumors Tumor cells killed by radiotherapy or chemotherapy release signaling molecules that stimulate both immune response and tumor aggressiveness; regulating these molecules could improve treatment efficacy. Tae Heung Kang, Yeong-Min Park, and co-workers at Konkuk University, Seoul, South Korea, have reviewed the role of damage-associated molecular patterns (DAMPs) in immunity and cancer. These signaling molecules act as danger signals, activating immune cells by binding to specific receptors. However, tumor cells have the same receptors, and DAMPs binding triggers chemoresistance and increases invasiveness. The researchers report that although DAMPs can trigger a helpful immune response, they can also cause chronic inflammation, which in turn promotes an immune suppression response, allowing tumors to escape immune detection. Improving our understanding of the functions of different DAMPs could improve our ability to boost the immune response and decrease tumor aggressiveness.
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- 2020
19. The role of tumor-derived exosomes in tumor immune escape: A concise review
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Khuong Duy Pham, Phuc Van Pham, Thao Nhi Huynh, and Nhat Chau Truong
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Angiogenesis ,chemical and pharmacologic phenomena ,Tumor-Derived ,Biology ,medicine.disease ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Microvesicles ,Metastasis ,law.invention ,Immune system ,law ,Cancer cell ,Cancer research ,medicine ,Suppressor ,Carcinogenesis - Abstract
Exosomes are small vesicles secreted by viable cells into the microenvironment. These vesicles bring various compositions, including lipids, RNAs and proteins, which carry information from producer cells to target cells. Cancer cells also produce exosomes, termed as tumor-derived exosomes (TDEs), which play important roles in immune modulation, angiogenesis and metastasis of tumors. This review summarizes the roles of TDEs in tumor immune escape mechanisms. TDEs affect all kinds of tumor-associated immune cells, including natural killer (NK) cells, dendritic cells (DCs), T and B lymphocytes, and myeloid-derived suppressor cells (MDSCs). Generally, TDEs suppress the immune system to promote tumor immune escape, thereby significantly contributing to tumorigenesis and metastasis.
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- 2020
20. Homogenous Magneto-Fluorescent Nanosensor for Tumor-Derived Exosome Isolation and Analysis
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Jingyun Guo, Chunzuan Xu, Taixue An, Bo Situ, Bo Li, Junjie Feng, Jianlei Shen, Weilun Pan, Chunchen Liu, Ye Zhang, Lei Zheng, Tingting Luo, and Wancheng Zheng
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Fluid Flow and Transfer Processes ,Chemistry ,Process Chemistry and Technology ,010401 analytical chemistry ,Liquid Biopsy ,Breast Neoplasms ,Bioengineering ,02 engineering and technology ,Integrated approach ,Tumor-Derived ,Exosomes ,021001 nanoscience & nanotechnology ,01 natural sciences ,Exosome ,Fluorescence ,Microvesicles ,0104 chemical sciences ,Magnetic isolation ,Nanosensor ,Biophysics ,Humans ,0210 nano-technology ,Instrumentation - Abstract
Tumor-derived exosomes carrying unique surface proteins have shown great promise as novel biomarkers for liquid biopsies. However, point-of-care analysis for tumor-derived exosomes in the blood with low-cost and easy processing is still challenging. Herein, we develop an integrated approach, homogenous magneto-fluorescent exosome (hMFEX) nanosensor, for rapid and on-site tumor-derived exosomes analysis. Tumor-derived exosomes are captured immunomagnetically, which further initiates the aptamer-triggered assembly of DNA three-way junctions in homogenous solution containing aggregation-induced emission luminogens and graphene oxide, resulting in an amplified fluorescence signal. By integrating magnetic isolation and enhanced fluorescence measurement, the hMFEX nanosensor detects tumor-derived exosomes in the dynamic range spanning 5 orders of magnitude with high specificity, and the limit of detection is 6.56 × 104 particles/μL. Analyzing tumor-derived exosomes in limited volume plasma from breast cancer patients demonstrates the excellent clinical diagnostic efficacy of the hMFEX nanosensor. This study provides new insights into the point-of-care testing of tumor-derived exosomes for cancer diagnostics.
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- 2020
21. Development of an In Vitro Assay to Assess Pharmacological Compounds and Reversion of Tumor-Derived Immunosuppression of Dendritic Cells
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Mikkel Møller Andersen, Jesper Larsen, Anders Elm Pedersen, Monika Gad, and Morten Hartvig Hansen
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0301 basic medicine ,Poor prognosis ,business.industry ,medicine.medical_treatment ,Immunology ,Reversion ,Cancer ,Immunosuppression ,General Medicine ,Tumor-Derived ,medicine.disease ,In vitro ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,business - Abstract
Cancer immunotherapies have achieved much success and have become the forefront treatment of cancers previously associated with poor prognosis. However, a major challenge in cancer immunotherapies ...
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- 2020
22. Triptolide decreases tumor‐associated macrophages infiltration and M2 polarization to remodel colon cancer immune microenvironment via inhibiting tumor‐derived CXCL12
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Guangyi Gao, Jiasheng Zhao, Wei Wang, Chao Gao, Xuan Jiang, and Gang Cao
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Male ,0301 basic medicine ,Physiology ,Colorectal cancer ,medicine.medical_treatment ,Clinical Biochemistry ,Down-Regulation ,Apoptosis ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Tumor-Associated Macrophages ,Tumor Microenvironment ,Animals ,Humans ,Medicine ,Cytotoxicity ,Cell Proliferation ,Mice, Inbred BALB C ,Tumor microenvironment ,business.industry ,NF-kappa B ,Cell Biology ,Immunotherapy ,Phenanthrenes ,Tumor-Derived ,Triptolide ,medicine.disease ,Chemokine CXCL12 ,Vascular endothelial growth factor ,RAW 264.7 Cells ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Cancer research ,Epoxy Compounds ,Diterpenes ,business ,HT29 Cells - Abstract
Colon cancer is a common and deadly human digestive tract malignant tumor with poor prognosis. Immunotherapy has elicited tremendous success as a treatment modality for multiple solid tumors. Triptolide is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F which shows various pharmacological actions including antitumor, anti-inflammatory, antimicrobial, antifibrosis, and antirheumatic. However, the influence of triptolide treatment on remodeling tumor immune microenvironment is still unknown in colon cancer. This study was aimed to investigate the therapeutic effect of triptolide treatment on colon cancer and the impact on tumor immune microenvironment and its underlying mechanism. We used CT26 subcutaneous tumors to conduct in vivo experiments and HT29, CT16, and Raw264.7 cells to perform in vitro assays. Triptolide had a therapeutic effect against colon cancer in vivo. Triptolide treatment distinctly inhibited the proliferation of colon cancer cells and induced apoptosis in vitro. In colon cancer immune microenvironment, triptolide treatment decreased the infiltration of tumor-associated macrophages through downregulating tumor-derived CXCL12 expression via nuclear factor kappa B and extracellular signal-regulated protein kinases 1 and 2 axis to remodel the immune microenvironment. Triptolide-educated colon cancers retarded the macrophages polarize to anti-inflammatory M2 status by decreasing the expression of Arg-1, CD206, and interleukin-10. Moreover, triptolide inhibited the migration of colon cancer cells via decreasing vascular endothelial growth factor expression. Our results identified the role of triptolide treatment in remodeling colon cancer immune microenvironment along with the distinct cytotoxicity function against colon cancer cells, which may provide the evidence for triptolide treatment in clinical.
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- 2020
23. Tumor-Derived EV-Encapsulated miR-181b-5p Induces Angiogenesis to Foster Tumorigenesis and Metastasis of ESCC
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Jiqiang Lu, Dongping Li, Jialiang Hu, Ying Wang, Lin Chen, Huan Bian, Hanmei Xu, and Chunlei Xia
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0301 basic medicine ,Angiogenesis ,medicine.disease_cause ,Article ,Metastasis ,angiogenesis ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,microRNA ,medicine ,metastasis ,PTEN ,neoplasms ,biology ,business.industry ,lcsh:RM1-950 ,miR-181b-5p ,Extracellular vesicle ,Tumor-Derived ,medicine.disease ,digestive system diseases ,esophageal squamous cell carcinoma ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Cancer research ,Molecular Medicine ,extracellular vesicle ,prognosis ,Carcinogenesis ,business - Abstract
Pathological angiogenesis is necessary for tumor development and metastasis. Tumor-derived extracellular vesicles (EVs) play an important role in mediating the crosstalk between cancer cells and vascular endothelial cells. To date, whether and how microRNAs (miRNAs) encapsulated in tumor-derived EVs affect angiogenesis in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that miR-181b-5p, an angiogenesis-promoting miRNA of ESCC, can be transferred from ESCC cells to vascular endothelial cells via EVs. In addition, ESCC-derived EVs-miR-181b-5p dramatically induced angiogenesis by targeting PTEN and PHLPP2, and thereby facilitated tumor growth and metastasis. Moreover, miR-181b-5p was highly expressed in ESCC tissues and serum EVs. High miR-181b-5p expression level in ESCC patients was well predicted for poor overall survival. Our work suggests that intercellular crosstalk between tumor cells and vascular endothelial cells is mediated by tumor-derived EVs. miR-181b-5p-enriched EVs secreted from ESCC cells are involved in angiogenesis that control metastasis of ESCC, providing a potential diagnostic biomarker or drug target for ESCC patients.
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- 2020
24. Tumor-derived exosomes facilitate tumor cells escape from drug therapy in clear cell renal cell carcinoma
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Mingdian Tan, Xiaogang Wang, Renfang Xu, Qianqian Shi, Yunjie Cao, Li Cui, Pengfeng Gong, Kai Wang, and Xiaozhou He
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Cancer Research ,drug resistance ,clear cell renal cell carcinoma (ccRCC) ,business.industry ,mammalian target of rapamycin (mTOR) ,Tumor cells ,Tumor-Derived ,Exosomes ,medicine.disease ,Microvesicles ,Clear cell renal cell carcinoma ,Pharmacotherapy ,Oncology ,Cancer research ,Medicine ,Original Article ,Radiology, Nuclear Medicine and imaging ,business - Abstract
Background Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent cancers in renal cancer patients. Currently, mTOR and vascular endothelial growth factor (VEGF) inhibitors are the main targets of clinical drugs used to treat ccRCC. However, the major clinical challenge with these treatments is drug resistance. So far, the mechanisms of drug resistance in cancer are not fully understood. Methods We applied tumor-derived exosomes to treat renal cells to detect the survival rate after co-treated with anti-tumor drugs—TNFα, mammalian target of rapamycin (mTOR) inhibitor or STAT3 inhibitor. Meanwhile, we also detected the expression change in the protein level related to the proliferation and exosome secretion. Results Exosomes derived from renal carcinoma cells facilitate resistance in tumors cells when given drug therapy via the mTOR-ERK-STAT-NF-κB signaling pathway. Conclusions Our results provide new insights on tumor cells resistance to drug therapies in general, and that exosomes could be the potential targets in treatment of ccRCC in future clinical therapy.
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- 2020
25. MicroRNA-106a suppresses prostate cancer proliferation, migration and invasion by targeting tumor-derived IL-8
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Hao Zeng, Ronggui Tao, Junru Chen, Sha Zhu, Jiyu Yang, Jindong Dai, Pengfei Shen, Xingming Zhang, Jinge Zhao, Peng Zhao, and Guangxi Sun
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Cancer Research ,business.industry ,Tumor-Derived ,medicine.disease ,interleukin-8 (IL-8) ,Prostate cancer ,Oncology ,miR-106a ,microRNA ,Cancer research ,Medicine ,Original Article ,Radiology, Nuclear Medicine and imaging ,progression ,Interleukin 8 ,business ,Prostate cancer (PCa) - Abstract
Background Tumor-derived interleukin-8 (IL-8) promotes tumorigenesis and progression of prostate cancer (PCa). MicroRNAs (miRNAs) are noncoding regulatory RNAs and their dysregulation is known to be implicated in carcinogenesis. However, the post-transcriptional mechanism of IL-8 via miRNAs is not fully understood. This study was intended to investigate whether miR-106a could affect the progression of PCa via targeting IL-8 or not. Methods Using bioinformatics analysis, we postulated that IL-8 might be post-transcriptionally regulated by miR-106a. This was validated by dual reporter gene assays that miR-106a could bind to the predicted site of IL-8 mRNA. To determine the biological effects of miR-106a on PCa cells (PC-3 and DU145), MTT, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), migration and invasion assays were performed. Results We found that miR-106a was barely expressed in PCa cells, whereas IL-8 was aberrantly upregulated. Elevated miR-106a could reduce IL-8 expression by directly binding the 3'-UTR of IL-8. Overexpression of miR-106a in PCa cells triggered cell apoptosis and suppressed cell proliferation, migration, and invasion. Conclusions This research showed that miR-106a could function as a tumor-suppressor by decreasing IL-8 levels in PCa.
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- 2020
26. Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4
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Dong Ha Kim, Chae Won Lee, Seon Ye Kim, Miyong Yun, Sang-Yeob Kim, Chang-Min Choi, Young-Su Yi, Yun Jung Choi, H.R. Kim, Jae Cheol Lee, Jin Kyung Rho, Sojung Park, Ki Jung Sung, and Young Hoon Sung
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Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Angiogenesis ,Muscle Proteins ,Apoptosis ,Mice, SCID ,Exosomes ,Exosome ,Metastasis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,microRNA ,Biomarkers, Tumor ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Cell Proliferation ,Neovascularization, Pathologic ,Cell growth ,business.industry ,Cancer ,Tumor-Derived ,Prognosis ,medicine.disease ,Xenograft Model Antitumor Assays ,Microvesicles ,respiratory tract diseases ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,business - Abstract
Tumor-derived exosomes (TEXs) contain enriched miRNAs that act as novel non-invasive biomarkers for cancer diagnosis and play a role in cancer progression. We investigated the exosomal miRNAs that affect cancer progression in non-small cell lung cancer (NSCLC) and identified the specific molecules involved. We identified that specific miRNAs in NSCLC cell-released exosomes can modulate angiogenesis, among which miR-619-5p was the most potent inducer. RCAN1.4 was identified as a target of miR-619-5p and its suppression promoted angiogenesis. Furthermore, the suppression of RCAN1.4 induced cell proliferation and metastasis in NSCLC cells. In patients with NSCLC, the level of RCAN1.4 expression was significantly lower, and that of miR-619-5p significantly higher, in tumor than normal lung tissues. miR-619-5p expression was higher than normal in exosomes isolated from the plasma of NSCLC patients. Finally, hypoxic conditions induced miR-619-5p upload into NSCLC cell-derived exosomes. Our findings indicate that exosomal miR-619-5p promotes the growth and metastasis of NSCLCs by regulating RCAN1.4 and can serve as a diagnostic indicator for these lung cancers.
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- 2020
27. Abstract P6-10-11: In vitro chemo interrogation of viable circulating tumor associated cells from breast cancer patients
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Cynthe Sims, Vineet Datta, Dadasaheb Akolkar, Viwek Mane, Madhavi Apastamb, Sachin Apurwa, Ajay Srinivasan, Ashok Gawai, Tim Crook, Revati Patil, Sanket Patil, Rajan Datar, and Vishakha Mhase
- Subjects
Drug ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Drug resistance ,Tumor-Derived ,medicine.disease ,In vitro ,On cells ,Breast cancer ,Internal medicine ,Cancer cell ,Medicine ,business ,Cytotoxicity ,media_common - Abstract
Background: Chemoresistance in cancer cells is the underlying reason for treatment failure. Real-time monitoring of chemoresistance and response (CRR) is a fundamental but unmet prerequisite of precision oncology. Repetitive invasive biopsies to obtain tumor tissue for in-vitro CRR profiling are neither feasible nor advisable. Circulating Tumor Associated Cells (C-TACs) have been proposed for functional assessment of CRR. In this observational study, we performed CRR profiling on viable C-TACs from breast cancer patients. Methods: In this 3 arm study, viable C-TACs were harvested from 15 ml of peripheral blood obtained from 242 breast cancer patients using CellWizard™, an epigenetically active media with paradoxical cytotoxicity that selectively kills normal cells and simultaneously confers survival benefit on cells of tumorigenic origin. C-TACs were stained with EPCAM, CK, CD45 and GCDFP. Viable Tumor Derived Cells (TDCs) harvested from freshly biopsied tumor tissue (Arm 1, N=48) and concurrently obtained C-TACs were simultaneously CRR profiled irrespective of whether patient was pre-treated or otherwise. Arm 2 (N=100) included refractory (pre-treated) patients where C-TACs were evaluated for resistance to previously administered drugs. Arm 3 (N=124) included recently diagnosed therapy naïve patients where C-TACs were evaluated for innate chemoresistance. Results: In Arm 1, CRR profile of C-TACs showed 96.1% concordance with CRR profile of concurrently obtained TDCs. In Arm2, CRR profiling of C-TACs identified chemoresistance due to prior drug exposure in 91.4% of patients. In Arm 3, innate chemoresistance was observed in 42% of patient samples towards commonly used first / second line Standard of Care drugs belonging to various functional categories such as mitotic inhibitors, DNA damaging agents, topo inhibitors and antimetabolites. Conclusion: This study shows for the first time the feasibility of CRR profiling of C-TACs and its correlation to in-vitro and in-vivo CRR characteristics of the tumor. Adoption of C-TAC based CRR profiling can provide unprecedented real time treatment oversight towards treatment selection and monitoring of drug resistance for personalized treatment of breast cancer patients. Citation Format: Timothy Crook, Dadasaheb Akolkar, Sanket Patil, Vishakha Mhase, Revati Patil, Cynthe Sims, Vineet Datta, Sachin Apurwa, Viwek Mane, Ashok Gawai, Madhavi Apastamb, Ajay Srinivasan, Rajan Datar. In vitro chemo interrogation of viable circulating tumor associated cells from breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-11.
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- 2020
28. Increased expression of PDGFA and RAF1 in tumor-derived exosomes in human colorectal cancer
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hadi ahmadi amoli, Leili Saeednejad Zanjani, Zahra Madjd, margot zoeller, Yuzhen Gao, Marzieh Naseri, Somayeh Vafaei, Marzieh Ebrahimi, and razieh karamnia
- Subjects
Colorectal cancer ,medicine ,Cancer research ,Tumor-Derived ,Biology ,medicine.disease ,Microvesicles - Abstract
Background: Overexpression of tumor markers in Extracellular vesicles (EV), especially in tumor-derived exosomes (TDEs), is implicated in metastasis. However, identifying the specific content of Ev's roles in CRC diagnosis or prognosis requires further validation by bioinformatics and clinical investigations. Methods: In the current study, we explored molecular markers shared between TDEs and circulating tumor cells (CTCs) in the blood of cancer patients to identify candidate genes involved in CRC metastasis. Common markers were analyzed in gene expression profiles of two studies (GSE31023 and GSE72577). Results: In blood samples from 20 CRC patients, the expression of candidate genes was assessed by real-time PCR in CTC, TDEs, and microvesicles (MVs), and the expression levels were correlated with clinicopathological features. To further confirm, the expression of candidate genes was investigated in exosomes derived from the parental HT-29 colorectal cancer cell line (HT-29-EXOs), and CSC-enriched spheroids (CSC-EXOs) derived thereof. Gene ontology (GO) analysis suggested platelet-derived growth factor A (PDGFA) and proto-oncogene, Serine/Threonine kinase Raf-1 (RAF1) as new CRC candidate markers in CTCs and TDEs. According to real-time PCR, expression of PDGFA (P=0.0086) and RAF1 (P=0.048) were upregulated in TDEs but significantly decreased (P=0.0001) in MVs. Furthermore, expression in CSC-EXOs (P=0.0004) was increased compared to HT-29-EXOs. Conclusion: PDGFA and RAF1 mRNA are higher in CSC-EXOs than in HT-29-EXOs, which correlates with higher expression in CSC than the primary tumor. Notably, as no increase was observed in MVs, PDGFA and RAF1 mRNA appear to be actively recruited into TDE.
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- 2022
29. The role of tumor-derived exosomes in tumor angiogenesis and tumor progression
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Marta Struga, Miroslaw J. Szczepanski, Shafaq M. Mirza, Katarzyna Piszczatowska, Alicja Głuszko, and Ireneusz Kantor
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0301 basic medicine ,Pharmacology ,Tumor angiogenesis ,tumor-derived exosomes ,business.industry ,hypoxia ,Pharmacology toxicology ,General Medicine ,Tumor-Derived ,Biochemistry ,Microvesicles ,endothelial cells ,03 medical and health sciences ,angiogenesis ,030104 developmental biology ,0302 clinical medicine ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,business ,Molecular Biology - Abstract
Exosomes, belonging to the group of extracellular bodies, are released by healthy as well as cancerous cells and serve as a communication pathway. Tumor-derived exosomes (TEX) possess the capacity to reprogram the function of normal cells owing to their genetic and molecular cargo. Such exosomes target endothelial cells (among others) in the tumor microenvironment to promote angiogenesis. Blood supply is essential in solid tumor growth and metastasis. The potential of pro-angiogenic changes is enhanced by an increased amount of circulating tumor-derived exosomes in the body fluids of cancer patients. A vascular network is important, since the proliferation, as well as the metastatic spread of cancer cells depends on an adequate supply of oxygen and nutrients, and the removal of waste products. New blood vessels and lymphatic vessels are formed through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. Thousands of patients have received anti-angiogenic therapy to date. Despite their theoretical efficacy, anti-angiogenic treatments have not proved beneficial in terms of long-term survival. Tumor-derived exosomes carrying pro-angiogenic factors might be a target for new anti-cancer therapy.
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- 2019
30. β-Sheet Richness of the Circulating Tumor-Derived Extracellular Vesicles for Noninvasive Pancreatic Cancer Screening
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Mdrakibhasan Khan, Qian Wen, Rick J. Jansen, Ang Guo, Aaron Bauer, Wenjie Xia, Komila Rasuleva, Santhalingam Elamurugan, Preston Steen, Zhaofan Li, Sijo Mathew, and Dali Sun
- Subjects
Immunoprecipitation ,Beta sheet ,Bioengineering ,Proteomics ,Article ,collective attribute ,Extracellular Vesicles ,Pancreatic cancer ,Cancer screening ,medicine ,Biomarkers, Tumor ,Humans ,protein structure ,Instrumentation ,Early Detection of Cancer ,Fluid Flow and Transfer Processes ,Chemistry ,Process Chemistry and Technology ,Cancer ,PDAC ,Tumor-Derived ,medicine.disease ,Pancreatic Neoplasms ,β-sheet ,Cancer research ,Biomarker (medicine) ,Protein Conformation, beta-Strand - Abstract
Tumor-derived extracellular vesicles (EVs) are under intensive study for their potential as noninvasive diagnosis biomarkers. Most EV-based cancer diagnostic assays trace supernumerary of a single cancer-associated marker or marker signatures. These types of biomarker assays are either subtype-specific or vulnerable to be masked by high background signals. In this study, we introduce using the β-sheet richness (BR) of the tumor-derived EVs as an effective way to discriminate EVs originating from malignant and nonmalignant cells, where EV contents are evaluated as a collective attribute rather than single factors. Circular dichroism, Fourier transform infrared spectroscopy, fluorescence staining assays, and a de novo workflow combining proteomics, bioinformatics, and protein folding simulations were employed to validate the collective attribute at both cellular and EV levels. Based on the BR of the tumorous EVs, we integrated immunoprecipitation and fluorescence labeling targeting the circulating tumor-derived EVs in serum and developed the process into a clinical assay, named EvIPThT. The assay can distinguish patients with and without malignant disease in a pilot cohort, with weak correlations to prognosis biomarkers, suggesting the potential for a cancer screening panel with existing prognostic biomarkers to improve overall performance.
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- 2021
31. The microenvironment of DLBCL is characterized by noncanonical macrophages recruited by tumor-derived CCL5
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Michel Aurrand-Lions, Mélanie Quintero, Christian Righini, Jean-François Mayol, Nathalie Sturm, Benoit Manfroi, Sébastien Tabruyn, Jérôme Moreaux, Bertrand Huard, Maria De Grandis, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
CCR1 ,Chemokine ,[SDV]Life Sciences [q-bio] ,Biology ,medicine.disease_cause ,CCL5 ,Monocytes ,Leukocyte Count ,stomatognathic system ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Tumor Microenvironment ,Neoplasm ,Humans ,skin and connective tissue diseases ,Chemokine CCL5 ,Lymphoid Neoplasia ,Macrophages ,Hematology ,Gene signature ,Tumor-Derived ,medicine.disease ,Germinal Center ,Lymphoma ,Cancer research ,biology.protein ,Lymphoma, Large B-Cell, Diffuse ,Carcinogenesis ,hormones, hormone substitutes, and hormone antagonists - Abstract
Key Points CCL5 is differentially expressed by DLBCL cells and efficiently recruits TAMs through their expression of CCR1/CCR5.Most DLBCL TAMs have a noncanonical gene signature., Visual Abstract, Tissue invasion by tumor cells induces a host inflammatory response that variably impacts tumorigenesis. This has been well documented for tumor-associated macrophages (TAMs) that could play a pro/M2- or an anti/M1-tumoral function. TAMs frequently infiltrate diffuse large B-cell lymphoma (DLBCL), an aggressive neoplasm arising from germinal center–experienced B cells. However, the pathway leading to the presence of TAMs in DLBCL remains unknown, and their impact is unclear. Here, we show that some DLBCL tumor cells expressed the chemokine CCL5, enabling the differential recruitment of blood monocytes through their expression of CCR1 and CCR5. CCL5 expression by DLBCL was not related to molecular subtypes, and healthy tonsillar B cells did not produce this chemokine, implying a posttransformation event. A single-cell analysis revealed that most DLBCL TAMs had a noncanonical gene signature with the concomitant expression of M1 and M2 genes. The presence of noncanonical TAMs may explain the lack of impact of macrophages on DLBCL development reported in some survival studies.
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- 2021
32. 667 Tumor-derived alpha-fetoprotein requires polyunsaturated fatty acids for immuno-metabolic dysregulation
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Paul Munson, Juraj Adamik, and Lisa H. Butterfield
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Pharmacology ,chemistry.chemical_classification ,Cancer Research ,Immunology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Tumor-Derived ,Oncology ,Biochemistry ,chemistry ,Molecular Medicine ,Immunology and Allergy ,Alpha-fetoprotein ,RC254-282 ,Polyunsaturated fatty acid - Abstract
BackgroundHepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide.1 The immuno-regulatory environment of the liver, coupled with tumor-specific immuno-suppressive mechanisms, has negatively impacted the development of clinically effective immunotherapies. Most HCC tumors secrete alpha-fetoprotein (AFP), which we previously demonstrated inhibited monocyte to dendritic cell (DC) differentiation and metabolism.2 3 These immunoregulatory effects depended upon a previously unidentified low molar mass ligand bound to tumor-derived (tAFP) but not cord-blood-derived 'normal' AFP (nAFP). To delineate the mechanism, we identified and tested fatty acids (FA) unique to tAFP necessary for immunosuppression.MethodsFatty acids bound to samples of ovalbumin (OVA), nAFP, and tAFP (n=3 each), were quantified by mass spectrometry and gas chromatography by the UCSD Lipidomics Core. Analysis of the single-cell metabolism was measured using the SCENITH assay4 via spectral-flow cytometry. Bulk measurement of metabolism was measured by microarray and glucose/lactate quantification of supernatants during monocyte to DC differentiation in vitro. Lastly, several fatty acids (FAs) were co-incubated with ligand-free preparations of OVA, nAFP, and tAFP to determine which FAs contribute to limiting DC differentiation in vitro.ResultsSCENITH analysis revealed a stark increase in lactate secretion and a marked switch from oxidative-phosphorylation (OXPHOS) to glycolysis in tAFP-treated DCs, which correlated with reduced co-stimulatory marker expression and increased PD-L1. g:Profiler analysis of microarray data confirmed dysregulation of FA metabolism. We identified three polyunsaturated fatty acids (PUFAs) that were enriched on tAFP by mass-spectrometry and gas chromatography. Screening of FAs on ligand-free preparations revealed two PUFAs on tAFP were uniquely able to decrease differentiation of iDC and mDCs in vitro.ConclusionsWe have identified unique FA ligands of tAFP and determined specific FAs that restore its immunoregulatory activities. To our knowledge, these are the first data demonstrating a role of a novel PUFA in inhibiting DC formation and are consistent with previous reports showing arachidonic (20:4) inhibits DC formation in vitro.5 Furthermore, we have identified key metabolic pathways of the immuno-metabolic dysregulation of DCs in HCC. These findings identify targets for strategies to reverse the tAFP induced immuno-metabolic dysfunction in vivo could be a strategy to potentiate robust anti-tumor immunity and improve survival in HCC patients.AcknowledgementsWe wish to acknowledge the Parker Institute for Cancer Immunotherapy, Dr. Oswald Quehenberger and Milda Simonaitis of the UCSD Lipid omics Core for their consultation on the lipid panel, as well as Vin Nguyen of the UCSF Flow Cytometry Core for his assistance with the flow cytometry panels.ReferencesSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin 2021;71:209–49. https://doi.org/10.3322/caac.21660.Pardee AD, Shi J, Butterfield LH. Tumor-Derived α-Fetoprotein Impairs the differentiation and T Cell stimulatory activity of human dendritic cells. J Immunol 2014;193:5723–32. https://doi.org/10.4049/jimmunol.1400725.Santos PM, Menk AV, Shi J, Tsung A, Delgoffe GM, Butterfield LH. Tumor-Derived α-Fetoprotein suppresses fatty acid metabolism and oxidative phosphorylation in dendritic cells. Cancer Immunol Res 2019;7:1001–12. https://doi.org/10.1158/2326-6066.cir-18-0513.Argüello RJ, Combes AJ, Char R, Gigan J-P, Baaziz AI, Bousiquot E, et al. SCENITH: a flow cytometry-based method to functionally profile energy metabolism with single-cell resolution. Cell Metab 2020;32:1063–1075.e7. https://doi.org/10.1016/j.cmet.2020.11.007.Zeyda M, Säemann MD, Stuhlmeier KM, Mascher DG, Nowotny PN, Zlabinger GJ, et al. Polyunsaturated fatty acids block dendritic cell activation and function independently of NF-κB activation. J Biol Chem 2005;280:14293–301. https://doi.org/10.1074/jbc.m410000200.Ethics ApprovalThe Cancer Immunotherapeutics Tissue Use Committee approved samples from healthy donors at UCSF.
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33. Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
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Akira Shibuya, Nanako Nishiyama, Hitoshi Koizumi, Kazumasa Kanemaru, Yuta Nakazawa, and Chigusa Nakahashi-Oda
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Mouse ,Endosome ,QH301-705.5 ,media_common.quotation_subject ,Science ,Inflammation ,chemical and pharmacologic phenomena ,T-Lymphocytes, Regulatory ,General Biochemistry, Genetics and Molecular Biology ,Extracellular Vesicles ,Mice ,Immunology and Inflammation ,immunoreceptor ,medicine ,Animals ,dendritic cells ,Receptors, Immunologic ,Biology (General) ,Internalization ,Cancer Biology ,media_common ,Tumor microenvironment ,General Immunology and Microbiology ,Chemistry ,tumor-infiltrating regulatory T cells ,General Neuroscience ,Melanoma ,hemic and immune systems ,General Medicine ,Extracellular vesicle ,Tumor-Derived ,medicine.disease ,IFN-b ,Mice, Inbred C57BL ,Transplantation ,Cancer research ,Medicine ,CD300a ,medicine.symptom ,tumor-derived extracellular vesicles ,Research Article - Abstract
Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice. Coculture of DCs with tumor-derived EV (TEV) induced the internalization of CD300a and the incorporation of EVs into endosomes, in which CD300a inhibited TEV-mediated TLR3–TRIF signaling for activation of the IFN-β-Treg cells axis. We also show that higher expression of CD300A was associated with decreased tumor-infiltrating Treg cells and longer survival time in patients with melanoma. Our findings reveal the role of TEV and CD300a on DCs in Treg cell activation in the tumor microenvironment.
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- 2021
34. The Role of Tumor-Derived Exosomes (TEX) in Shaping Anti-Tumor Immune Competence
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Theresa L. Whiteside
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Adenosine ,QH301-705.5 ,T cell ,Cell ,Biology ,Exosomes ,Models, Biological ,Article ,Immune system ,Neoplasms ,microRNA ,medicine ,Animals ,Humans ,tumor-derived exosomes (TEX) ,tumor microenvironment (TME) ,Biology (General) ,Tumor microenvironment ,General Medicine ,Tumor-Derived ,Microvesicles ,medicine.anatomical_structure ,adenosinergic pathway ,Cancer research ,immune suppression ,extracellular vesicles (EVs) ,Reprogramming ,Signal Transduction - Abstract
Emerging studies suggest that extracellular vesicles (EVs) mediating intercellular communication in the tumor microenvironment (TME) play a key role in driving cancer progression. Tumor-derived small EVs or exosomes (TEX) enriched in immunosuppressive proteins or in microRNAs targeting suppressive pathways in recipient cells contribute to reprogramming the TME into a cancer-promoting milieu. The adenosinergic pathway is an acknowledged major contributor to tumor-induced immune suppression. TEX carry the components of this pathway and utilize ATP to produce adenosine (ADO). TEX-associated ADO emerges as a key factor in the suppression of T cell responses to therapy. Here, the significance of the ADO pathway in TEX is discussed as a highly effective mechanism of cancer-driven immune cell suppression and of resistance to immune therapies.
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- 2021
35. Author response: Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
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Chigusa Nakahashi-Oda, Akira Shibuya, Hitoshi Koizumi, Nanako Nishiyama, Kazumasa Kanemaru, and Yuta Nakazawa
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Chemistry ,Tumor-Derived ,Inhibitory postsynaptic potential ,Extracellular vesicles ,Cell biology - Published
- 2021
36. Tumor-derived exosomal PD-L1 in progression of cancer and immunotherapy
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Erfan Rezazadeh Gavgani, Reza Majidazar, Parya Seraji, Parisa Lotfinejad, Mobina Oladghaffari, Seyed Ziaedin Rasihashemi, and Tohid Kazemi
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Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Exosomes ,B7-H1 Antigen ,PD-L1 ,Neoplasms ,medicine ,Immune Tolerance ,Humans ,Immunologic Factors ,biology ,business.industry ,Cancer ,Cell Biology ,Immunotherapy ,Tumor-Derived ,medicine.disease ,Microvesicles ,Immune checkpoint ,Biomarker (cell) ,Cancer research ,biology.protein ,Antibody ,business - Abstract
Cancer is a gravely important health issue all over the world and has been spreading fast. In recent years immune checkpoint treatment options have been used extensively as a primary line of treatment for different cancer types. PD-1 and its ligand, PD-L1, are members of the immune-checkpoints superfamily. Anti-PD-L1 and anti-PD-1 antibodies have shown efficacy against different cancer types, but fewer than 30% of patients have shown robust therapeutic responses and, therefore, it is hypothesized that exosomal PD-L1 is the mechanism to blame for failure in primary immune checkpoint therapy. The identical membrane topology of exosomal PD-L1 with tumor cell membrane-type provides the possibility to mimic immunosuppressive effects of tumor cell membrane PD-L1. In this review, it is discussed whether exosomal PD-L1 binds to antibodies and hence resistance to immunotherapy will be developed, and targeting exosome biogenesis inhibition can provide a new strategy to overcome tumor resistance to anti-PD-L1 therapy. Diagnostic and prognostic values of exosomal PD-L1 in different cancer types are discussed. Multiple clinical studies conclude that the level of tumor-derived exosomes (TEXs) as a biomarker for diagnosis could distinguish cancer patients from healthy controls. Elevated exosomal PD-L1 levels may be predictive of advanced disease stages, cancer metastasis, lower response to anti-PD-1/PD-L1 therapy, lower overall survival rates, and poor tumor prognosis. These novel findings of TEXs serve as promising therapeutic targets for early diagnosis and prevention of cancer progression.
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- 2021
37. Tumor-Derived Extracellular Vesicles: A Means of Co-opting Macrophage Polarization in the Tumor Microenvironment
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Jeffrey S. Schorey, Theodore Reed, and Crislyn D'Souza-Schorey
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polarization ,Cell type ,Tumor microenvironment ,QH301-705.5 ,Chemistry ,Mini Review ,Macrophage polarization ,Cell Biology ,Tumor-Derived ,Phenotype ,macrophages ,Cell biology ,Cell and Developmental Biology ,Immune system ,Tumor progression ,intercellular communication ,Nucleic acid ,tumor microenvironment ,Biology (General) ,extracellular vesicles ,Developmental Biology - Abstract
Extracellular vesicles (EVs) are a heterogeneous population of membrane-bound parcels of bioactive proteins, nucleic acids, and lipids released from almost all cell types. The diversity of cargo packaged into EVs proffer the induction of an array of effects on recipient cells. EVs released from tumor cells have emerged as a vital means of communication and immune modulation within the tumor microenvironment (TME). Macrophages are an important contributor to the TME with seemingly paradoxical roles promoting either pro- or anti-tumoral immune function depending on their activated phenotypes. Here, we discuss the influence of tumor-derived extracellular vesicles on the functional plasticity of macrophages in tumor progression.
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- 2021
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38. Effects of Tumor-Derived Exosome Programmed Death Ligand 1 on Tumor Immunity and Clinical Applications
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Bo Shao, Qin Dang, Zhuang Chen, Chen Chen, Quanbo Zhou, Bingbing Qiao, Jinbo Liu, Shengyun Hu, Guixian Wang, Weitang Yuan, and Zhenqiang Sun
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PD-L1 ,Tumor microenvironment ,Chemistry ,QH301-705.5 ,T cell ,Cell Biology ,Review ,Tumor-Derived ,Exosome ,Microvesicles ,Immune checkpoint ,Immune tolerance ,tumor immunity ,Cell and Developmental Biology ,Immune system ,medicine.anatomical_structure ,PD-1 ,Cancer research ,medicine ,exosome ,biomarker ,Biology (General) ,Developmental Biology - Abstract
Programmed death ligand 1 (PD-L1) is a typical immune surface protein that binds to programmed cell death 1 (PD-1) on T cells through its extracellular domain. Subsequently, T cell activity is inhibited, and tumor immune tolerance is enhanced. Anti-PD-1/PD-L1 immune checkpoint therapy blocks the combination of PD-1/PD-L1 and rejuvenates depleted T cells, thereby inhibiting tumor growth. Exosomes are biologically active lipid bilayer nanovesicles secreted by various cell types, which mediate signal communication between cells. Studies have shown that PD-L1 can not only be expressed on the surface of tumor cells, immune cells, and other cells in the tumor microenvironment, but also be released from tumor cells and exist in an extracellular form. In particular, exosome PD-L1 plays an unfavorable role in tumor immunosuppression. The immunomodulatory effect of exosome PD-L1 and its potential in fluid diagnosis have attracted our attention. This review aims to summarize the available evidence regarding the biological characteristics of exosome PD-L1 in tumor immunity, with a particular focus on the mechanisms in different cancers and clinical prospects. In addition, we also summarized the current possible and effective detection methods for exosome PD-L1 and proposed that exosome PD-L1 has the potential to become a target for overcoming anti-PD-1/PD-L1 antibody treatment resistance.
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- 2021
39. Tumor-Derived Biomimetic Nanozyme With Immune Evasion Ability For Synergistically Enhanced Low Dose Radiotherapy
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Chunyu Huang, Wei Liu, Liang Du, Mingzhu Chen, Yongfa Zheng, and Zeming Liu
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Immune system ,business.industry ,Cancer research ,Medicine ,Tumor-Derived ,Low dose radiotherapy ,Evasion (ethics) ,business - Abstract
High doses of radiation can cause serious side effects and drug resistance, high-performance radiosensitizers are urgently needed. To overcome this issue, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for use in combination with low-dose RT. CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH) and peroxidase activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2Gy) can provide a substantial suppression of tumor proliferation. To summarize, this is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.
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- 2021
40. Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration
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Yong Li, Yexi Chen, Chaoyu Xie, Hongmei Dong, Jiehua Zheng, Yusheng Lin, Xijiao Pang, Xiurong Ke, Hao Zhang, Yuchen Jiang, Kai Li, and Xiao Xiong
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tumor-derived exosomes ,Chemistry ,QH301-705.5 ,macrophage polarization ,Phosphatase ,Macrophage polarization ,invasion and migration ,Cell Biology ,Protein tyrosine phosphatase ,Tumor-Derived ,medicine.disease ,stat ,Microvesicles ,Cell and Developmental Biology ,Breast cancer ,breast cancer ,Cancer research ,medicine ,Macrophage ,Biology (General) ,protein tyrosine phosphatase receptor type O ,Developmental Biology ,Original Research - Abstract
Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer.
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- 2021
41. The effects of tumor‐derived exosomes on T‐cell function and efficacy of cancer immunotherapy
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Yuanyuan Hao, Wenbin Qian, Yanping Shao, Panpan Chen, Yang Xu, and Xuzhao Zhang
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Tumor microenvironment ,medicine.anatomical_structure ,Cancer immunotherapy ,Chemistry ,medicine.medical_treatment ,T cell ,General Engineering ,medicine ,Cancer research ,Immunotherapy ,Tumor-Derived ,Microvesicles ,Function (biology) - Published
- 2021
42. Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal
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Eugenio Zoni, Benjamin T Spike, Peter C. Gray, David S. Salomon, Elisa Rodrigues Sousa, Sofia Karkampouna, Marianna Kruithof-de Julio, and David W. Freeman
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QH301-705.5 ,610 Medicine & health ,Review ,Biology ,CRIPTO ,Cripto ,medicine.disease_cause ,Catalysis ,Metastasis ,Inorganic Chemistry ,Paracrine signalling ,stem cells ,Transforming Growth Factor beta ,medicine ,cancer ,metastasis ,Animals ,Humans ,Neoplastic transformation ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Organic Chemistry ,fibrosis ,EMT ,Cancer ,therapeutic target ,General Medicine ,Tumor-Derived ,medicine.disease ,Computer Science Applications ,Chemistry ,Carcinogenesis ,Neuroscience ,Transforming growth factor ,Signal Transduction - Abstract
There exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more than a century, their clinical utility has yet to be fully realized1. This review highlights the small signaling protein CRIPTO encoded by the tumor derived growth factor 1 (TDGF1/Tdgf1) gene, an oft cited oncofetal protein whose presence in the cancer literature as a tumor promoter, diagnostic marker and viable therapeutic target continues to grow. We touch lightly on features well established and well-reviewed since its discovery more than 30 years ago, including CRIPTO’s early developmental roles and modulation of SMAD2/3 activation by a selected set of transforming growth factor β (TGF-β) family ligands. We predominantly focus instead on more recent and less well understood additions to the CRIPTO signaling repertoire, on its potential upstream regulators and on new conceptual ground for understanding its mode of action in the multicellular and often stressful contexts of neoplastic transformation and progression. We ask whence it re-emerges in cancer and where it ‘hides’ between the time of its fetal activity and its oncogenic reemergence. In this regard, we examine CRIPTO’s restriction to rare cells in the adult, its potential for paracrine crosstalk, and its emerging role in inflammation and tissue regeneration—roles it may reprise in tumorigenesis, acting on subsets of tumor cells to foster cancer initiation and progression. We also consider critical gaps in knowledge and resources that stand between the recent, exciting momentum in the CRIPTO field and highly actionable CRIPTO manipulation for cancer therapy and beyond.
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- 2021
43. Tumor-Derived Extracellular Vesicles: Modulation of Cellular Functional Dynamics in Tumor Microenvironment and Its Clinical Implications
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Nathalia Leal Santos, Silvina Odete Bustos, Darshak Bhatt, Roger Chammas, and Luciana Nogueira de Sousa Andrade
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Cell signaling ,Tumor microenvironment ,Stromal cell ,QH301-705.5 ,Angiogenesis ,Chemistry ,Mini Review ,cell communication ,tumor progression ,Extracellular vesicle ,Cell Biology ,Tumor-Derived ,medicine.disease ,Metastasis ,Cell and Developmental Biology ,Tumor progression ,Cancer research ,medicine ,tumor microenvironment ,Biology (General) ,extracellular vesicles ,functional dynamics ,Developmental Biology - Abstract
Cancer can be described as a dynamic disease formed by malignant and stromal cells. The cellular interaction between these components in the tumor microenvironment (TME) dictates the development of the disease and can be mediated by extracellular vesicles secreted by tumor cells (TEVs). In this review, we summarize emerging findings about how TEVs modify important aspects of the disease like continuous tumor growth, induction of angiogenesis and metastasis establishment. We also discuss how these nanostructures can educate the immune infiltrating cells to generate an immunosuppressive environment that favors tumor progression. Furthermore, we offer our perspective on the path TEVs interfere in cancer treatment response and promote tumor recurrence, highlighting the need to understand the underlying mechanisms controlling TEVs secretion and cargo sorting. In addition, we discuss the clinical potential of TEVs as markers of cell state transitions including the acquisition of a treatment-resistant phenotype, and their potential as therapeutic targets for interventions such as the use of extracellular vesicle (EV) inhibitors to block their pro-tumoral activities. Some of the technical challenges for TEVs research and clinical use are also presented.
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- 2021
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44. A pancreas tumor derived organoid study: from drug screen to precision medicine
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Yongcui Mao, Lawrence Atteh, Pinyan Liu, Man Yang, Xun Li, Jia Yao, and Wenbo Meng
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0301 basic medicine ,Drug ,Cancer Research ,endocrine system diseases ,Pancreatic ductal adenocarcinoma (PDAC) ,medicine.medical_treatment ,media_common.quotation_subject ,Pancreas tumor derived organoids (PTOs) ,Review ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Drug screen ,Pancreatic tumor ,Pancreatic cancer ,Genetics ,medicine ,RC254-282 ,Pancreas cancer ,media_common ,QH573-671 ,business.industry ,Precision medicine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Tumor-Derived ,medicine.disease ,digestive system diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Personalized medicine ,Cytology ,Pancreas ,business - Abstract
Pancreatic ductal adenocarcinoma (PDAC) one of the deadliest malignant tumor. Despite considerable progress in pancreatic cancer treatment in the past 10 years, PDAC mortality has shown no appreciable change, and systemic therapies for PDAC generally lack efficacy. Thus, developing biomarkers for treatment guidance is urgently required. This review focuses on pancreatic tumor organoids (PTOs), which can mimic the characteristics of the original tumor in vitro. As a powerful tool with several applications, PTOs represent a new strategy for targeted therapy in pancreatic cancer and contribute to the advancement of the field of personalized medicine.
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- 2021
45. Current insights into the expression and functions of tumor-derived immunoglobulins
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Hui Peng, Juping Wang, Shulin Yang, Anna Nong, Xiangsheng Wu, Jing Zhao, Jie Gao, Liying Chen, Hao Zhang, and Haoming Hua
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Cancer Research ,Immunology ,Review Article ,Computational biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Immunoediting ,RC254-282 ,QH573-671 ,biology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Diagnostic markers ,Diagnostic marker ,Cell Biology ,Tumor-Derived ,Expression (mathematics) ,Human tumor ,030220 oncology & carcinogenesis ,biology.protein ,Stem cell ,Signal transduction ,Antibody ,Cytology ,030215 immunology - Abstract
Numerous studies have reported expressions of immunoglobulins (Igs) in many human tumor tissues and cells. Tumor-derived Igs have displayed multiple significant functions which are different from classical Igs produced by B lymphocytes and plasma cells. This review will concentrate on major progress in expressions, functions, and mechanisms of tumor-derived Igs, similarities and differences between tumor-derived Igs and B-cell-derived Igs. We also discuss the future research directions of tumor-derived Igs, including their structural characteristics, physicochemical properties, mechanisms for rearrangement and expression regulation, signaling pathways involved, and clinical applications.
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- 2021
46. Characterization and Functional Analysis of Tumor‐Derived Microparticles
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Jingwei Ma, Huafeng Zhang, Bo Huang, Ke Tang, and Keke Wei
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congenital, hereditary, and neonatal diseases and abnormalities ,Tumor microenvironment ,Cell type ,General Immunology and Microbiology ,Functional analysis ,Chemistry ,General Neuroscience ,nutritional and metabolic diseases ,Health Informatics ,Tumor cells ,Cell Communication ,Tumor-Derived ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,Medical Laboratory Technology ,Immune system ,Cell-Derived Microparticles ,Neoplasms ,Tumor Microenvironment ,Humans ,Immunotherapy ,General Pharmacology, Toxicology and Pharmaceutics ,skin and connective tissue diseases ,Intracellular ,Function (biology) - Abstract
Microparticles (MPs) are heterogeneous populations of cell-derived vesicles that play an important role in intercellular communications. The release of MPs by tumor cells is a very common event in tumor microenvironments (TMEs). Tumor cell-derived MPs (T-MPs) contain a variety of bioactive molecules, thus modulating various biological processes, including the regulation of immune cell phenotype and function, as well as immune responses. Moreover, T-MPs can be used as natural carriers to deliver therapeutic drugs into tumor cells and immune cells, thus remodeling TMEs and modifying anti-tumor immune responses. These features allow T-MPs to function as potential biomaterials to be applied in tumor immunotherapies and vaccines. This article describes protocols for the isolation of T-MPs from supernatants of cultured tumor cells by multi-step centrifugations. Tools and protocols are also provided in order to characterize and validate the isolated MPs and to analyze the interaction between T-MPs and different target cells. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation of tumor cell-derived microparticles by multi-step centrifugations Basic Protocol 2: Characterization and validation of tumor cell-derived microparticles Basic Protocol 3: Functional analysis of the uptake of tumor cell-derived microparticles by different cell types.
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- 2021
47. Full SNO 2021 Abstracts PDF
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Adam Grippin, Sheila Carrera-Justiz, Frances Weidert, Héctor R. Méndez-Gómez, James McGuiness, Duane Mitchell, and Elias J Sayour
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Cancer Research ,Small interfering RNA ,Myeloid ,business.industry ,Immunogenicity ,Brain tumor ,Cancer ,Tumor-Derived ,medicine.disease ,medicine.anatomical_structure ,Immune system ,Oncology ,Glioma ,Cancer research ,Medicine ,Neurology (clinical) ,Full SNO 2021 Abstracts PDF ,business - Abstract
Background: Since the preponderance of pediatric gliomas are mutationally 'bland,' immune checkpoint inhibitors are unlikely to mediate therapeutic benefit. Alternately, immunologic response can be induced de novo against pediatric gliomas with mRNA cancer vaccines. Messenger RNA represents a paradigm shift in vaccinology (i.e. COVID-19) given its flexibility, commercialization, and propensity to confer rapid protection with only a single vaccine. Objective: We sought to develop a new mRNA platform with an optimized backbone for insertion of both personalized and/or “off the shelf” (i.e. H3K27M) transcripts for rapid induction of anti-tumor activity against pediatric gliomas. Approach: We synthesized an mRNA backbone with optimized 5' and 3' UTRs for delivery of gene transcripts pertinent to pediatric brain tumors using a lipid-nanoparticle (NP) delivery vehicle. This vaccine utilizes a novel engineering design that layers tumor derived mRNA into a lipid-nanoparticle (NP) “onion-like” or multi-lamellar package. Results: We demonstrate immunogenicity of RNA-NPs delivering either personalized glioma mRNA or H3K27M mRNA. RNA-NPs localize to myeloid cells in murine KR158b brain tumors and activate dendritic cells that supplant regulatory intratumoral myeloid populations inducing antigenrecall response with long-term survivor benefit. Our optimized mRNA backbone yielded significantly improved anti-tumor efficacy compared with commercial backbones. We have shown this approach can be refined for co-delivery of immunomodulatory RNAs (i.e. GM-CSF) and/or delivery of siRNAs targeting immunoregulatory axes (PD-L1) in murine brain tumors (GL261). We have since established safety of RNA-NPs in acute/chronic murine GLP toxicity studies without cross-reactivity to normal-brain, and launched a large-animal canine brain tumor trial which demonstrated RNANPs to be feasible, safe and immunologically active. Conclusion: RNA-NPs reprogram the brain tumor microenvironment while inducing a gliomaspecific immune response. We have since received FDA-IND approval for first-in-human trials.
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- 2021
48. 腫瘍融解アデノウイルスでの局所治療後に分泌される腫瘍由来細胞外小胞はアブスコパル効果を引き起こす
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Nobuhiko Kanaya, Tomoko Tsumura, Ryoma Sugimoto, Toshiyoshi Fujiwara, Satoru Kikuchi, Masashi Hashimoto, Yasuo Urata, Hiroshi Tazawa, Kento Kumon, Masahiko Nishizaki, Shinji Kuroda, Yuki Hamada, Yoshihiko Kakiuchi, Chiaki Yagi, and Shunsuke Kagawa
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Oncolytic adenovirus ,Cell Survival ,Drug delivery system ,Abscopal effect ,Exosome ,Adenoviridae ,Extracellular Vesicles ,Mice ,Systemic delivery ,Cell Line, Tumor ,Drug Discovery ,Genetics ,Cytotoxic T cell ,Animals ,Humans ,Molecular Biology ,Pharmacology ,Chemistry ,Autophagy ,Local treatment ,Liver Neoplasms ,Tumor-Derived ,HCT116 Cells ,Xenograft Model Antitumor Assays ,Oncolytic virus ,Oncolytic Viruses ,Viral Tropism ,Apoptosis ,Colonic Neoplasms ,Cancer research ,Molecular Medicine ,Original Article - Abstract
Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.
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- 2021
49. CD44v3 as a biomarker of tumor derived exosomes in HNSCC patient’s plasma
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T L Whiteside, Tk. Hoffmann, Pj. Schuler, M-N Theodoraki, Cornelia Brunner, and Simon Laban
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business.industry ,Cancer research ,Biomarker (medicine) ,Medicine ,Tumor-Derived ,business ,Microvesicles - Published
- 2021
50. The Effect of Mechanical Stretch on Myotube Growth Suppression by Tumor‐derived Factors
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Brittany R. Counts, James A. Carson, and Jessica L. Halle
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Growth suppression ,Chemistry ,Genetics ,Tumor-Derived ,Molecular Biology ,Biochemistry ,Biotechnology ,Cell biology - Published
- 2021
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