7 results on '"Shao, Chen-Yang"'
Search Results
2. Microenvironment‐Responsive Prodrug‐Induced Pyroptosis Boosts Cancer Immunotherapy
- Author
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Yao Xiao, Tian Zhang, Xianbin Ma, Qi‐Chao Yang, Lei‐Lei Yang, Shao‐Chen Yang, Mengyun Liang, Zhigang Xu, and Zhi‐Jun Sun
- Subjects
immunotherapy ,paclitaxel ,prodru gs ,pyroptosis ,tumor microenvironment ,Science - Abstract
Abstract The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage‐associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor‐specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual‐responsive system facilitates the nano‐prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo‐photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo‐photodynamic therapy and control‐release PTX synergistically induce gasdermin E (GSDME)‐related pyroptosis. It is speculated that inspired chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency.
- Published
- 2021
- Full Text
- View/download PDF
3. Immunogenic hypofractionated radiotherapy sensitising head and neck squamous cell carcinoma to anti-PD-L1 therapy in MDSC-dependent manner
- Author
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Liang Mao, Jun-Jie Zhou, Yao Xiao, Qi-Chao Yang, Shao-Chen Yang, Shuo Wang, Zhi-Zhong Wu, Hong-Gang Xiong, Hai-Jun Yu, and Zhi-Jun Sun
- Subjects
Cancer Research ,Oncology - Published
- 2023
4. Long Non-coding RNA LINC02195 as a Regulator of MHC I Molecules and Favorable Prognostic Marker for Head and Neck Squamous Cell Carcinoma
- Author
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Hao Li, Hong-Gang Xiong, Yao Xiao, Qi-Chao Yang, Shao-Chen Yang, Hong-Chao Tang, Wen-Feng Zhang, and Zhi-Jun Sun
- Subjects
lncRNA ,MHC ,TCGA ,tumor microenvironment ,T cell ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The loss of major histocompatibility complex class I (MHC I) molecules is an important mechanism by which cancer cells escape immunosurveillance in head and neck squamous cell carcinoma (HNSCC). Several long non-coding RNAs (lncRNAs) have been implicated in immune response and regulation including antigen processing and presentation. However, few studies on lncRNAs regulating MHC I expression in HNSCC have been conducted. In this study, MHC I related lncRNAs were identified from the The Cancer Genome Atlas (TCGA) HNSCC database. One of the lncRNAs, long intergenic non-protein coding RNA 2195 (LINC02195), was found to be associated with genes encoding MHC I molecules and patient prognosis in the TCGA database. KEGG and GO analyses suggested that LINC02195 was closely related to antigen processing and presentation. qRT-PCR revealed high expression of LINC02195 in human HNSCC tissues and HNSCC cell lines compared with normal mucosal tissues. in situ hybridization of the HNSCC tissue microarray revealed a correlation between high LINC02195 expression and a favorable prognosis in our patient cohort. Silencing of LINC02195 decreased MHC I protein expression, as evidenced by western blotting. Multiplex immunochemistry was performed to reveal the positive correlation between high LINC02195 expression and an increased number of CD8+ and CD4+ T cells in the tumor microenvironment. Based on our study, LINC02195 is a promising prognostic marker and a target for future therapeutic interventions.
- Published
- 2020
- Full Text
- View/download PDF
5. pH-responsive nanoprodrugs combining a Src inhibitor and chemotherapy to potentiate antitumor immunity via pyroptosis in head and neck cancer
- Author
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Su-Wen Zhu, Mengjie Ye, Xianbin Ma, Zhi-Zhong Wu, Shu-Cheng Wan, Shao-Chen Yang, Hao Li, Zhigang Xu, and Zhi-Jun Sun
- Subjects
Squamous Cell Carcinoma of Head and Neck ,Biomedical Engineering ,Dasatinib ,Antineoplastic Agents ,General Medicine ,Hydrogen-Ion Concentration ,Biochemistry ,Biomaterials ,Oxaliplatin ,Mice ,Head and Neck Neoplasms ,Cell Line, Tumor ,Tumor Microenvironment ,Humans ,Animals ,Prodrugs ,Molecular Biology ,Biotechnology - Abstract
As the prominent feature of the development and progression of head and neck squamous cell carcinoma (HNSCC) is immunosuppression, therapeutic strategies to restore antitumor immunity have shown promising prospects. The efficacy of chemotherapy, a mainstay in HNSCC treatment, is exemplified by cytotoxic effects as well as immunostimulation, whereas compensatory activation of prosurvival signals in tumor tissues may compromise its efficacy. Aberrant activation of Src is present in many human malignancies including HNSCC, and is implicated in chemotherapy resistance. In this regard, tumor-microenvironment-responsive prodrug nanomicelles (PDO NPs) are rationally designed to combine chemotherapy (oxaliplatin, OXA) and Src inhibitors (dasatinib, DAS) for HNSCC therapy. PDO NPs are constructed by chemically modifying small-molecule prodrugs (DAS-OXA) loaded in block copolymer iPDPA with pH-triggered transforming capability. PDO NPs can controllably release drugs in response to tumor acidity, thus increasing tumor accumulation and therapeutic efficacy. Moreover, PDO NPs can elicit pyroptosis of tumor cells and induce T-cell-mediated antitumor immunity in murine HNSCC models. In summary, nanoprodrugs integrating Src inhibitors enhance the immunological effects of chemotherapy and provide insight into promising approaches for augmenting immunochemotherapy for HNSCC. STATEMENT OF SIGNIFICANCE: In this study, pH-responsive nanomicelles (PDO NPs) were constructed by loading a small molecular prodrug synthesized by the Src inhibitor dasatinib and the chemotherapy drug oxaliplatin into the amphiphilic block copolymer iPDPA to improve the immunological effects of chemotherapy for HNSCC. These nanomicelles can efficiently accumulate in tumor cells and achieve pH-responsive drug release. The PDO NPs can induce pyroptosis of tumor cells and potentiate antitumor immunity in subcutaneous and syngenetic orthotopic HNSCC mouse models, which may present a promising strategy to enhance immunochemotherapy for HNSCC.
- Published
- 2022
6. Microenvironment‐Responsive Prodrug‐Induced Pyroptosis Boosts Cancer Immunotherapy
- Author
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Qi-Chao Yang, Zhi-Jun Sun, Xianbin Ma, Lei-Lei Yang, Zhigang Xu, Mengyun Liang, Yao Xiao, Tian Zhang, and Shao-Chen Yang
- Subjects
General Chemical Engineering ,medicine.medical_treatment ,Science ,General Physics and Astronomy ,Medicine (miscellaneous) ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,chemistry.chemical_compound ,Mice ,paclitaxel ,Cancer immunotherapy ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,prodru gs ,Animals ,tumor microenvironment ,General Materials Science ,Prodrugs ,Research Articles ,chemistry.chemical_classification ,Reactive oxygen species ,Tumor microenvironment ,Mice, Inbred BALB C ,Photosensitizing Agents ,pyroptosis ,General Engineering ,Pyroptosis ,Immunotherapy ,Acquired immune system ,Antineoplastic Agents, Phytogenic ,Glutathione ,Immune checkpoint ,Disease Models, Animal ,Drug Liberation ,chemistry ,Paclitaxel ,Photochemotherapy ,Colonic Neoplasms ,Cancer research ,Female ,immunotherapy ,Reactive Oxygen Species ,Research Article - Abstract
The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage‐associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor‐specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual‐responsive system facilitates the nano‐prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo‐photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo‐photodynamic therapy and control‐release PTX synergistically induce gasdermin E (GSDME)‐related pyroptosis. It is speculated that inspired chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency., A smart tumor microenvironmental reactive oxygen species/glutathione dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel and photosensitizer purpurin 18 loading is designed. Chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment the efficiency of immune checkpoint blockade therapy.
- Published
- 2021
7. Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy
- Author
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Zhigang Xu, Peng Xue, Tian Zhang, Yao Xiao, Xiaoxiao Shi, Zhi-Jun Sun, Shao-Chen Yang, Yuejun Kang, Xianbin Ma, Qi-Chao Yang, Shuo Wang, and Gang Liu
- Subjects
medicine.medical_treatment ,OXA, oxaliplatin ,ITM, immunosuppressive tumor microenvironment ,MCHC, mean corpuscular hemoglobin concentration ,5-ALA, 5-aminolevulinic acid ,HGB, hemoglobin concentration ,CPT-11, irinotecan ,Nanogel ,DTT, d,l-dithiothreitol ,0302 clinical medicine ,CRT, calreticulin ,Cancer immunotherapy ,HCPT, 10-hydroxy camptothecin ,WBC, white blood cell count ,LYM, lymphocyte ratio ,GSH, glutathione ,Medicine ,DM NGs, doxorubicin-based mannose nanogel ,ICB, immune checkpoint blockade ,MFI, mean fluorescence intensity ,General Pharmacology, Toxicology and Pharmaceutics ,RBC, red blood cell count ,Prodrug ,0303 health sciences ,MAN, mannose ,ICG, indocyanine Green ,LDH, lactate dehydrogenase ,TME, tumor microenvironment ,Ce6, chlorin e6 ,FCM, flow cytometry ,irAEs, immune-related adverse events ,TAAs, tumor-associated antigens ,DOC, docetaxel ,030220 oncology & carcinogenesis ,MCSs, multicellular spheroids ,Immunogenic cell death ,Original Article ,Immunotherapy ,APCs, antigen-presenting cells ,DCs, dendritic cells ,Bioresponsive ,ALKP, alkaline phosphatase ,TMA, tissue microarrays ,IHC, immunohistochemistry ,medicine.drug ,ATP, adenosine triphosphate ,CRE, creatinine ,FDA, Fluorescein diacetate ,CLSM, confocal laser scanning microscope ,H&E, hematoxylin-eosin ,ICD, immunogenic cell death ,RM1-950 ,AUC, area under curves ,TAM, tumor-associated macrophages ,03 medical and health sciences ,Immune system ,HCT, hematocrit ,ALT, alanine aminotransferase ,DLN, draining lymph nodes ,TGF-β, transforming growth factor-β ,MPV, mean platelet volume ,Chemotherapy ,Doxorubicin ,GEM, gemcitabine ,030304 developmental biology ,P18, purpurin 18 ,Tumor microenvironment ,business.industry ,PLT, platelets ,NGs, nanogels ,PDI, polydispersity index ,DOX, doxorubicin ,DDSs, drug delivery systems ,PTX, paclitaxel ,HMGB1, high migrating group box 1 ,Urea, urea nitrogen ,DAMPs, damage-associated molecular patterns ,Cancer research ,5-FU, 5-fluorouracil ,Therapeutics. Pharmacology ,AST, aminotransferase ,business ,Mannose ,RDW, variation coefficient of red blood cell distribution width - Abstract
The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines., Graphical abstract Engineering DOX-based mannose nanogel via GSH-sensitive –SS– bond crosslinker was reported, which not only destroyed the glycolysis process of tumor cells, but also induced robust immunogenic cell death against tumors.Image 1
- Published
- 2021
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