293 results on '"Nößner E"'
Search Results
52. Dissociation of beta 2-microglobulin from HLA class I heavy chains correlates with acquisition of epitopes in the cytoplasmic tail.
- Author
-
Little, A M, primary, Nössner, E, additional, and Parham, P, additional
- Published
- 1995
- Full Text
- View/download PDF
53. Species-specific differences in chaperone interaction of human and mouse major histocompatibility complex class I molecules.
- Author
-
Nössner, E, primary and Parham, P, additional
- Published
- 1995
- Full Text
- View/download PDF
54. The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.
- Author
-
Friberg A, Thumann S, Hennig J, Zou P, Nössner E, Ling PD, Sattler M, and Kempkes B
- Subjects
- Adult, Amino Acid Sequence, Blotting, Western, Crystallography, X-Ray, Epstein-Barr Virus Nuclear Antigens genetics, Fluorescent Antibody Technique, HeLa Cells, Humans, Immunoenzyme Techniques, Immunoprecipitation, Molecular Sequence Data, Mutant Proteins genetics, Mutation genetics, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Protein Multimerization, Protein Structure, Tertiary, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Viral Proteins genetics, Epstein-Barr Virus Nuclear Antigens chemistry, Mutant Proteins chemistry, Trans-Activators genetics, Transcriptional Activation, Viral Proteins chemistry
- Abstract
Epstein-Barr virus (EBV) is a γ-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2) is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END) domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four β-strands and an α-helix which form a parallel dimer by interaction of two β-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the α-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics.
- Published
- 2015
- Full Text
- View/download PDF
55. Application and new findings of scRNA-seq and ST-seq in prostate cancer.
- Author
-
Li, Zhuang, Li, Zhengnan, Luo, Yuanyuan, Chen, Weiming, Fang, Yinyi, Xiong, Yuliang, Zhang, Qinyi, Yuan, Dongbo, Yan, Bo, and Zhu, Jianguo
- Abstract
Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world, which seriously threatens the life and health of middle-aged and elderly men. The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment. Understanding the mechanisms of prostate cancer pathogenesis and disease progression is important to guide diagnosis and therapy. The emergence of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) technologies has brought breakthroughs in the study of prostate cancer. It makes up for the defects of traditional techniques such as fluorescence-activated cell sorting that are difficult to elucidate cell-specific gene expression. This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq, aims to provide a reference for the optimal diagnosis and treatment of prostate cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
56. Revolutionizing the treatment for nasopharyngeal cancer: the impact, challenges and strategies of stem cell and genetically engineered cell therapies.
- Author
-
Chin-King Looi, Ee-Mun Loo, Heng-Chee Lim, Yik-Ling Chew, Kok-Yong Chin, Shiau-Chuen Cheah, Bey Hing Goh, and Chun-Wai Mai
- Subjects
CHIMERIC antigen receptors ,CANCER relapse ,TUMOR-infiltrating immune cells ,STEM cells ,T cells - Abstract
Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the nasopharynx and is consistently associated with the Epstein-Barr virus (EBV) infection. Its unique anatomical location and complex aetiology often result in advancedstage disease at first diagnosis. While radiotherapy (RT) and chemotherapy have been the mainstays of treatment, they often fail to prevent tumour recurrence and metastasis, leading to high rates of treatment failure and mortality. Recent advancement in cell-based therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown great promise in hematological malignancies and are now being investigated for NPC. However, challenges such as targeting specific tumour antigens, limited T cell persistence and proliferation, and managing treatment-related toxicities must be addressed. Extensive research is needed to enhance the effectiveness and safety of these therapies, paving the way for their integration into standard clinical practice for better management of NPC and a better quality of life for human health. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
57. Analysis of HLA-B35 variants andB35 haplotypes by isoelectric focusing and Southern blot analysis
- Author
-
Rudolf Wank, Dolores J. Schendel, Nössner E, and Lederer E
- Subjects
Gel electrophoresis ,Genetics ,Genetic Linkage ,Isoelectric focusing ,Immunology ,Haplotype ,Genetic Variation ,Immunogenetics ,Biology ,Molecular biology ,Blotting, Southern ,Haplotypes ,HLA-B Antigens ,Humans ,Isoelectric Focusing ,Restriction fragment length polymorphism ,DNA Probes ,Polymorphism, Restriction Fragment Length ,Southern blot - Published
- 1989
- Full Text
- View/download PDF
58. Definition of HLA class I-associated DNA polymorphisms using anHLA-B locus-derived cDNA probe
- Author
-
Nössner E, Lederer E, and Dolores J. Schendel
- Subjects
Immunology ,Genes, MHC Class I ,Class (philosophy) ,Immunogenetics ,Human leukocyte antigen ,Biology ,chemistry.chemical_compound ,HLA Antigens ,Sequence Homology, Nucleic Acid ,Complementary DNA ,Genetics ,Humans ,Gene ,Polymorphism, Genetic ,Nucleic Acid Hybridization ,DNA ,DNA Probes, HLA ,Molecular biology ,Human genetics ,Blotting, Southern ,chemistry ,HLA-B Antigens ,Restriction fragment length polymorphism ,Polymorphism, Restriction Fragment Length - Published
- 1989
- Full Text
- View/download PDF
59. Harnessing innate and adaptive immunity for adoptive cell therapy of renal cell carcinoma.
- Author
-
Geiger C, Nössner E, Frankenberger B, Falk CS, Pohla H, and Schendel DJ
- Subjects
- Animals, Dendritic Cells cytology, Dendritic Cells metabolism, Killer Cells, Natural cytology, Killer Cells, Natural metabolism, Models, Biological, T-Lymphocytes, Regulatory cytology, T-Lymphocytes, Regulatory metabolism, Carcinoma, Renal Cell immunology, Carcinoma, Renal Cell therapy, Immunity, Innate, Immunotherapy, Adoptive, Kidney Neoplasms immunology, Kidney Neoplasms therapy
- Abstract
The development of immunotherapies for renal cell carcinoma (RCC) has been the subject of research for several decades. In addition to cytokine therapy, the benefit of various adoptive cell therapies has again come into focus in the past several years. Nevertheless, success in fighting this immunogenic tumor is still disappointing. RCC can attract a multitude of different effector cells of both the innate and adaptive immune system, including natural killer (NK) cells, gammadelta T cells, NK-like T cells, peptide-specific T cells, dendritic cells (DC), and regulatory T cells (Tregs). Based on intensive research on the biology and function of different immune cells, we now understand that individual cell types do not act in isolation but function within a complex network of intercellular interactions. These interactions play a pivotal role in the efficient activation and function of effector cells, which is a prerequisite for successful tumor elimination. This review provides a current overview of the diversity of effector cells having the capacity to recognize RCC. Aspects of the functions and anti-tumor properties that make them attractive candidates for adoptive cell therapies, as well as experience in clinical application are discussed. Improved knowledge of the biology of this immune network may help us to effectively harness various effector cells, placing us in a better position to develop new therapeutic strategies to successfully fight RCC.
- Published
- 2009
- Full Text
- View/download PDF
60. A polyvalent cellular vaccine induces T-cell responses against specific self-antigens overexpressed in chronic lymphocytic B-cell leukemia.
- Author
-
Kronenberger K, Nössner E, Frankenberger B, Wahl U, Dreyling M, Hallek M, and Mocikat R
- Subjects
- Aged, Aged, 80 and over, Antigens, Neoplasm genetics, Autoantigens genetics, B-Lymphocytes immunology, Cancer Vaccines therapeutic use, DNA-Binding Proteins immunology, DNA-Binding Proteins metabolism, Dendritic Cells immunology, Dendritic Cells metabolism, Female, Humans, Immunotherapy, Active, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Male, Middle Aged, Proto-Oncogene Proteins c-bcl-2 immunology, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-mdm2 immunology, Proto-Oncogene Proteins c-mdm2 metabolism, Transcription Factors immunology, Transcription Factors metabolism, Antigens, Neoplasm immunology, Autoantigens immunology, B-Lymphocytes transplantation, Cancer Vaccines immunology, Leukemia, Lymphocytic, Chronic, B-Cell therapy, T-Lymphocytes, Cytotoxic immunology
- Abstract
B cell-derived chronic lymphocytic leukemia (CLL) is an incurable disease that requires innovative therapeutic regimens. Experimental approaches of immunotherapy aiming at induction of systemic T-cell responses have been developed. Trioma cells provide a potent vaccine derived from malignant B cells that allows multiple antigens (Ags) from the parental tumor to be ingested by Ag-presenting cells. Like other strategies using modified whole tumor cells, this approach induces polyvalent responses. Using trioma cell-pulsed dendritic cells (DCs) for T-cell activation in vitro, we asked whether specific Ags overexpressed by CLL can be identified as target structures of such responses and what is the nature of these Ags. Expression levels of several genes in CLL samples were quantitated by reverse transcriptase-polymerase chain reaction. T lymphocytes were polyvalently stimulated by trioma-pulsed DCs and specificities were tested by determining cytokine secretion in the presence of target cells transfected with RNA coding for those Ags that were found to be overexpressed. We demonstrate that DCs pulsed with the modified tumor cells efficiently activate T lymphocytes against CLL and that overexpressed Ags related to leukemogenesis, such as BCL-2, MDM2, and ETV5, serve as targets for those T cells. Immune escape by Ag loss or mutation is less likely to occur if immunity is directed against altered self-proteins that are involved in malignant transformation. Therefore, vaccines based on modified tumor cells such as triomas hold promise for immunotherapy of CLL and other malignancies. Polyvalent vaccines originally designed as individualized therapeutics may be more broadly applicable, at least in patients showing similar Ag patterns.
- Published
- 2008
- Full Text
- View/download PDF
61. Antitumor effector functions of T cells are dependent on in vivo priming and restricted T-cell receptor expression.
- Author
-
Lüking C, Kronenberger K, Frankenberger B, Nössner E, Röcken M, and Mocikat R
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Female, Flow Cytometry, Immunologic Memory, Interferon-gamma metabolism, Lymphocyte Activation, Lymphoma, B-Cell pathology, Mice, Mice, Inbred BALB C, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Antigen, T-Cell, alpha-beta genetics, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes metabolism, T-Lymphocytes pathology, Vaccination, Adoptive Transfer, Lymphoma, B-Cell immunology, Lymphoma, B-Cell prevention & control, Receptors, Antigen, T-Cell, alpha-beta immunology, T-Lymphocytes immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Tumor-specific T cells are crucial for immunologic control of malignant disease. T cells can be induced in vivo by vaccination or adoptively transferred after activation ex vivo. We investigated the requirements for generating T cells with optimal antitumor effector functions in a murine lymphoma model. Using adoptive transfer, we show that in vivo efficacy of T cells cannot be predicted by tumor reactivity in vitro. A restricted T-cell receptor beta chain repertoire of T-cell populations stimulated ex vivo against tumor cells was necessary but not sufficient for tumor protectivity. Tumor elimination furthermore required vaccination of donor mice, hence in vivo priming. The in vivo priming step may allow tumor-specific T cells to accumulate in vitro more rapidly and to survive for longer periods after withdrawal of the antigenic stimulus and adoptive transfer. A possible survival benefit of in vivo induced T cells may be ascribed to the responsiveness to homeostatic cytokines and to unique cytokine milieus encountered in vivo. Most importantly, monoclonal T cells cannot inhibit tumor growth. A prerequisite of tumor rejection was the expression of at least 2 T-cell receptor beta chains by transferred T-cell populations. This finding has implications for designing adoptive transfer strategies for the clinic., ((c) 2008 Wiley-Liss, Inc.)
- Published
- 2008
- Full Text
- View/download PDF
62. Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematologic and other malignancies.
- Author
-
Schuster IG, Busch DH, Eppinger E, Kremmer E, Milosevic S, Hennard C, Kuttler C, Ellwart JW, Frankenberger B, Nössner E, Salat C, Bogner C, Borkhardt A, Kolb HJ, and Krackhardt AM
- Subjects
- Antigens, Neoplasm immunology, Blotting, Western, Bone Marrow metabolism, Cell Line, Tumor, Clone Cells, Cytoskeletal Proteins metabolism, Enzyme-Linked Immunosorbent Assay, Epitopes, T-Lymphocyte immunology, Formins, HLA-A Antigens, Humans, Immunotherapy, Adoptive methods, Leukocytes, Mononuclear metabolism, Peptides immunology, Receptors, Antigen, T-Cell genetics, Reverse Transcriptase Polymerase Chain Reaction, Thymus Gland metabolism, Cytoskeletal Proteins immunology, Cytotoxicity, Immunologic, Hematologic Neoplasms immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Cell-based immunotherapy in settings of allogeneic stem cell transplantation or donor leukocyte infusion has curative potential, especially in hematologic malignancies. However, this approach is severely restricted due to graft-versus-host disease (GvHD). This limitation may be overcome if target antigens are molecularly defined and effector cells are specifically selected. We chose formin-related protein in leukocytes 1 (FMNL1) as a target antigen after intensive investigation of its expression profile at the mRNA and protein levels. Here, we confirm restricted expression in peripheral blood mononuclear cells (PBMCs) from healthy donors but also observe overexpression in different leukemias and aberrant expression in transformed cell lines derived from solid tumors. We isolated allorestricted T-cell clones expressing a single defined TCR recognizing a particular HLA-A2-presented peptide derived from FMNL1. This T-cell clone showed potent antitumor activity against lymphoma and renal cell carcinoma cell lines, Epstein-Barr virus (EBV)-transformed B cells, and primary tumor samples derived from patients with chronic lymphocytic leukemia (CLL), whereas nontransformed cells with the exception of activated B cells were only marginally recognized. Allorestricted TCRs with specificity for naturally presented FMNL1-derived epitopes may represent promising reagents for the development of adoptive therapies in lymphoma and other malignant diseases.
- Published
- 2007
- Full Text
- View/download PDF
63. Dendritic cell-based immunogens for B-cell chronic lymphocytic leukemia.
- Author
-
Allgeier T, Garhammer S, Nössner E, Wahl U, Kronenberger K, Dreyling M, Hallek M, and Mocikat R
- Subjects
- Aged, Aged, 80 and over, Antigens, CD analysis, Antigens, CD19 analysis, B7-1 Antigen analysis, B7-2 Antigen analysis, CD11c Antigen analysis, CD3 Complex analysis, CD5 Antigens analysis, Coculture Techniques, Dendritic Cells cytology, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, HLA-DR Antigens analysis, Humans, Hybrid Cells immunology, Immunoglobulins analysis, Interferon-gamma metabolism, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Male, Membrane Glycoproteins analysis, Microscopy, Fluorescence, Middle Aged, Tumor Necrosis Factor-alpha metabolism, CD83 Antigen, Dendritic Cells immunology, Leukemia, Lymphocytic, Chronic, B-Cell immunology
- Abstract
Hybrids generated from tumor cells and dendritic cells (DC) have been proposed as tools for treating malignant disease. Here, we study the underlying principles and the feasibility for the adjuvant therapy of human B cell chronic-lymphocytic leukemia (B-CLL). CLL cells and allogeneic DC were only mixed or additionally fused. Using a combination of FACS and fluorescence microscopic analyses, we show that DC-CLL hybrids can be successfully generated. However, fusion frequencies have to be critically evaluated because the number of fused cells is overestimated when based on FACS analyses alone. The capability of activating patients' PBMC was examined by measuring cytokine secretion in co-culture assays. We made a systematic comparison of the immunostimulatory capacities of different stimulator cell populations, including DC-CLL fusion samples, unfused mixtures of DC and CLL cells as well as DC or tumor cells alone. Surprisingly, even unfused mixtures had a pronounced tumor-directed immunostimulatory effect. This could be explained by the capture of antigens from surrounding leukemia cells by DC during co-cultivation. Although fusion frequencies were low, PBMC stimulation was significantly more effective when the mixtures were subjected to cell fusion. The most potent stimulus was provided by DC-CLL fusion samples derived from mature DC, probably due to their enhanced costimulatory capacity. In summary, DC-tumor cell hybrids might be feasible in the treatment of B-CLL. It should be considered that FACS analysis is not sufficient to assess fusion frequencies and that interactions between unfused DC and CLL cells also result in PBMC activation.
- Published
- 2007
- Full Text
- View/download PDF
64. Immunological Tumor Microenvironment of Solitary Fibrous Tumors—Associating Immune Infiltrate with Variables of Prognostic Significance.
- Author
-
Medina-Ceballos, Emilio, Machado, Isidro, Giner, Francisco, Blázquez-Bujeda, Álvaro, Espino, Mónica, Navarro, Samuel, and Llombart-Bosch, Antonio
- Subjects
MACROPHAGES ,CELL physiology ,SCIENTIFIC observation ,RETROSPECTIVE studies ,BIOCHIPS ,TUMOR markers ,EVALUATION of medical care ,MULTIVARIATE analysis ,LYMPHOCYTES ,IMMUNOHISTOCHEMISTRY ,MESENCHYME tumors ,RESEARCH ,DISEASE progression - Abstract
Simple Summary: Solitary fibrous tumors (SFTs) are tumors that can vary greatly in how they behave, with some being harmless while others become aggressive and life-threatening. This study evaluated 52 fusion-confirmed SFTs with clinical follow-up. The aim was to analyze the immune intratumoral infiltrate and correlate the presence of specific immune cells and risk stratification systems to see if the presence or absence of certain cells could help predict how the tumor will behave or correlate with other clinicopathologic characteristics. The research found that, while certain immune cells were associated with specific tumor features with prognostic significance, these immune cells did not reliably predict the tumor's overall risk level. This suggests that the immune environment within SFTs is complex and may not be useful on its own for determining the tumor progression risk. Nonetheless, the presented results give an insight into the relationship between immune tumor cells and histologic characteristics such as necrosis, proliferation index, and neoplastic cell morphology. Background and objectives: Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs). Methods: A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10–49, 2 = 50–99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round–oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS. Results: Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round–oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1. Conclusions: SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
65. Identification of cancer stem cell-related genes through single cells and machine learning for predicting prostate cancer prognosis and immunotherapy.
- Author
-
YaXuan Wang, Li Ma, Jiaxin He, HaiJuan Gu, and HaiXia Zhu
- Subjects
RANDOM forest algorithms ,CANCER stem cells ,REGULATOR genes ,PROSTATE cancer prognosis ,TREATMENT effectiveness ,PROSTATE cancer - Abstract
Background: Cancer stem cells (CSCs) are a subset of cells within tumors that possess the unique ability to self-renew and give rise to diverse tumor cells. These cells are crucial in driving tumormetastasis, recurrence, and resistance to treatment. The objective of this study was to pinpoint the essential regulatory genes associated with CSCs in prostate adenocarcinoma (PRAD) and assess their potential significance in the diagnosis, prognosis, and immunotherapy of patients with PRAD. Method: The study utilized single-cell analysis techniques to identify stem cellrelated genes and evaluate their significance in relation to patient prognosis and immunotherapy in PRAD through cluster analysis. By utilizing diverse datasets and employing various machine learning methods for clustering, diagnostic models for PRAD were developed and validated. The random forest algorithm pinpointed HSPE1 as the most crucial prognostic gene among the stem cellrelated genes. Furthermore, the study delved into the association between HSPE1 and immune infiltration, and employed molecular docking to investigate the relationship between HSPE1 and its associated compounds. Immunofluorescence staining analysis of 60 PRAD tissue samples confirmed the expression of HSPE1 and its correlation with patient prognosis in PRAD. Result: This study identified 15 crucial stem cell-related genes through singlecell analysis, highlighting their importance in diagnosing, prognosticating, and potentially treating PRAD patients. HSPE1 was specifically linked to PRAD prognosis and response to immunotherapy, with experimental data supporting its upregulation in PRAD and association with poorer prognosis. Conclusion: Overall, our findings underscore the significant role of stem cellrelated genes in PRAD and unveil HSPE1 as a novel target related to stem cell. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
66. The m6A regulators in prostate cancer: molecular basis and clinical perspective.
- Author
-
Yu Cao, Man Jia, Chunyan Duan, Zhihui Yang, Bo Cheng, and Ronghao Wang
- Subjects
ANDROGEN deprivation therapy ,RNA modification & restriction ,CELLULAR signal transduction ,WESTERN countries ,ADENOSINES - Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death among men in western countries. Evidence has indicated the significant role of the androgen receptor (AR) as the main driving factor in controlling the development of PCa, making androgen receptor inhibition (ARI) therapy a pivotal management approach. In addition, AR independent signaling pathways also contribute to PCa progression. One such signaling pathway that has garnered our attention is N6- Methyladenosine (m
6 A) signaling, which refers to a chemical modification on RNA with crucial roles in RNA metabolism and disease progression, including PCa. It is important to comprehensively summarize the role of each individual m6 A regulator in PCa development and understand its interaction with AR signaling. This review aims to provide a thorough summary of the involvement of m6 A regulators in PCa development, shedding light on their upstream and downstream signaling pathways. This summary sets the stage for a comprehensive review that would benefit the scientific community and clinical practice by enhancing our understanding of the biology of m6 A regulators in the context of PCa. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
67. The role of ncRNAs and exosomes in the development and progression of endometrial cancer.
- Author
-
Niebora, Julia, Wozniak, Sławomir, Domagała, Dominika, Data, Krzysztof, Farzaneh, Maryam, Zehtabi, Mojtaba, Gale Dari, Mahrokh Abouali, Pour, Fatemeh Khojasteh, Bryja, Artur, Kulus, Magdalena, Mozdziak, Paul, Dziegiel, Piotr, and Kempisty, Bartosz
- Subjects
LINCRNA ,CELL transformation ,NON-coding RNA ,GENE expression ,CANCER stem cells ,GYNECOLOGIC cancer - Abstract
Endometrial cancer (EC) is one of the most common gynecologic cancers. In recent years, research has focused on the genetic characteristics of the tumors to detail their prognosis and tailor therapy. In the case of EC, genetic mutations have been shown to underlie their formation. It is very important to know the mechanisms of EC formation related to mutations induced by estrogen, among other things. Noncoding RNAs (ncRNAs), composed of nucleotide transcripts with very low protein-coding capacity, are proving to be important. Their expression patterns in many malignancies can inhibit tumor formation and progression. They also regulate protein coding at the epigenetic, transcriptional, and posttranscriptional levels. MicroRNAs (miRNAs), several varieties of which are associated with normal endometrium as well as its tumor, also play a particularly important role in gene expression. MiRNAs and long noncoding RNAs (lncRNAs) affect many pathways in EC tissues and play important roles in cancer development, invasion, and metastasis, as well as resistance to anticancer drugs through mechanisms such as suppression of apoptosis and progression of cancer stem cells. It is also worth noting that miRNAs are highly precise, sensitive, and robust, making them potential markers for diagnosing gynecologic cancers and their progression. Unfortunately, as the incidence of EC increases, treatment becomes challenging and is limited to invasive tools. The prospect of using microRNAs as potential candidates for diagnostic and therapeutic use in EC seems promising. Exosomes are extracellular vesicles that are released from many types of cells, including cancer cells. They contain proteins, DNA, and various types of RNA, such as miRNAs. The noncoding RNA components of exosomes vary widely, depending on the physiology of the tumor tissue and the cells from which they originate. Exosomes contain both DNA and RNA and have communication functions between cells. Exosomal miRNAs mediate communication between EC cells, tumor-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and play a key role in tumor cell proliferation and tumor microenvironment formation. Oncogenes carried by tumor exosomes induce malignant transformation of target cells. During the synthesis of exosomes, various factors, such as genetic and proteomic data are upregulated. Thus, they are considered an interesting therapeutic target for the diagnosis and prognosis of endometrial cancer by analyzing biomarkers contained in exosomes. Expression of miRNAs, particularly miR-15a-5p, was elevated in exosomes derived from the plasma of EC patients. This may suggest the important utility of this biomarker in the diagnosis of EC. In recent years, researchers have become interested in the topic of prognostic markers for EC, as there are still too few identified markers to support the limited treatment of endometrial cancer. Further research into the effects of ncRNAs and exosomes on EC may allow for cancer treatment breakthroughs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
68. Prostate cancer stem cells and their targeted therapies.
- Author
-
Huilan Su, Liqun Huang, Jianjun Zhou, and Guosheng Yang
- Subjects
CANCER stem cells ,PROSTATE cancer ,STEM cell treatment ,CASTRATION-resistant prostate cancer ,ANDROGEN receptors ,CELL populations - Abstract
Prostate cancer (PCa) is the most common malignancy among men worldwide. Through androgen receptor signaling inhibitor (ARSI) treatment, patients eventually succumb to castration-resistant prostate cancer (CRPC). For this, the prostate cancer stem cells (PCSCs), as a minor population of tumor cells that can promote tumor relapse, ARSI resistance, and disease progression, are gaining attention. Therefore, specific therapy targeting PCSCs has momentum. This study reviewed the identification and characterization of PCSCs and PCSCbased putative biomarkers and summarized their mechanisms of action. We further discussed clinical trials of novel therapeutic interventions focused on PCSC-related pathways, the PCSC microenvironment, cutting-edge miRNA therapy, and immunotherapy approaches from a mechanistic standpoint. This review provides updated insights into PCSC plasticity, identifying new PCSC biomarkers and optimized treatments for patients with advanced PCa. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
69. Genome-Wide Identification and Interaction Analysis of Turbot Heat Shock Protein 40 and 70 Families Suggest the Mechanism of Chaperone Proteins Involved in Immune Response after Bacterial Infection.
- Author
-
Geng, Yuanwei, Gai, Yuxuan, Zhang, Yanping, Zhao, Shengwei, Jiang, Anlan, Li, Xueqing, Deng, Kaiqing, Zhang, Fuxuan, Tan, Lingling, and Song, Lin
- Subjects
PSETTA maxima ,HEAT shock proteins ,BINDING site assay ,BACTERIAL diseases ,MOLECULAR chaperones ,AEROMONAS salmonicida ,IMMUNE response - Abstract
Hsp40–Hsp70 typically function in concert as molecular chaperones, and their roles in post-infection immune responses are increasingly recognized. However, in the economically important fish species Scophthalmus maximus (turbot), there is still a lack in the systematic identification, interaction models, and binding site analysis of these proteins. Herein, 62 Hsp40 genes and 16 Hsp70 genes were identified in the turbot at a genome-wide level and were unevenly distributed on 22 chromosomes through chromosomal distribution analysis. Phylogenetic and syntenic analysis provided strong evidence in supporting the orthologies and paralogies of these HSPs. Protein–protein interaction and expression analysis was conducted to predict the expression profile after challenging with Aeromonas salmonicida. dnajb1b and hspa1a were found to have a co-expression trend under infection stresses. Molecular docking was performed using Auto-Dock Tool and PyMOL for this pair of chaperone proteins. It was discovered that in addition to the interaction sites in the J domain, the carboxyl-terminal domain of Hsp40 also plays a crucial role in its interaction with Hsp70. This is important for the mechanistic understanding of the Hsp40–Hsp70 chaperone system, providing a theoretical basis for turbot disease resistance breeding, and effective value for the prevention of certain diseases in turbot. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
70. Vaccination against B-cell chronic lymphocytic leukemia with trioma cells: preclinical evaluation.
- Author
-
Wahl U, Nössner E, Kronenberger K, Gangnus R, Pohla H, Staege MS, Kolb HJ, Hallek M, and Mocikat R
- Subjects
- Adult, Aged, Animals, Cancer Vaccines therapeutic use, Cell Line, Tumor, Chromosome Mapping, Cytokines analysis, Disease Models, Animal, Female, Flow Cytometry, Humans, Hybridomas immunology, In Situ Hybridization, Fluorescence, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Lymphocyte Activation, Lymphoma immunology, Male, Mice, Middle Aged, T-Lymphocytes immunology, Cancer Vaccines immunology, Leukemia, Lymphocytic, Chronic, B-Cell immunology
- Abstract
Purpose: Trioma cells are lymphoma cells that have been fused to a hybridoma and have thereby been modified to express an immunoglobulin directed against surface receptors of antigen-presenting cells. Trioma cells that potentially include all lymphoma-derived antigens will be targeted to professional antigen-presenting cells in vivo. This allows uptake, processing, and presentation of tumor-derived antigens to T lymphocytes. In a mouse model, vaccination with trioma cells conferred long-lasting, T cell-dependent tumor immunity and was even able to eradicate established lymphomas. Here, we investigated whether this potent approach is effective in the human system., Experimental Design: Malignant cells from 11 patients with B cell chronic-lymphocytic leukemia (B-CLL) were fused to an anti-Fc receptor hybridoma. The resulting trioma cells were extensively characterized with respect to their clonal origin. The induction of autologous tumor-specific T lymphocytes in the presence of trioma and antigen-presenting cells was examined in vitro by determining cytokine secretion in coculture assays., Results: In seven cases, trioma cells could successfully be generated from B-CLL cells. Stimulation of autologous lymphocytes with trioma cells induced a leukemia-specific T-cell response. Immunostimulatory trioma cells were also obtained from two patients with solid B-cell lymphoma., Conclusions: Trioma-mediated immunization may be a promising adjuvant treatment of human malignancies of the B-cell lineage, particularly of B-CLL, which has still a very poor prognosis. Our in vitro results pave the way for clinical application.
- Published
- 2003
71. The role of heat shock protein (hsp70) in dendritic cell maturation: hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors.
- Author
-
Kuppner MC, Gastpar R, Gelwer S, Nössner E, Ochmann O, Scharner A, and Issels RD
- Subjects
- Antigens, CD metabolism, Cells, Cultured, Coculture Techniques, Dendritic Cells immunology, Dendritic Cells metabolism, Flow Cytometry, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, HSP70 Heat-Shock Proteins metabolism, Humans, Immunophenotyping, Interferon-gamma metabolism, Interleukin-4 pharmacology, Monocytes metabolism, Stem Cells cytology, Stem Cells drug effects, Stem Cells metabolism, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic metabolism, Time Factors, Cell Differentiation drug effects, Dendritic Cells cytology, Dendritic Cells drug effects, HSP70 Heat-Shock Proteins pharmacology, Monocytes cytology, Monocytes drug effects
- Abstract
Members of the heat shock protein (hsp70) family are either constitutively expressed (hsc70) or can be induced by hyperthermic stress (hsp70). Recombinant hsp70 (rhsp70) stimulates cytokine production from monocytes and enhances NK cell proliferation and cytotoxicity. Here we demonstrate that rhsp70 binds to immature dendritic cells (DC) derived from monocyte precursors and induces their maturation as evidenced by an increase in CD40, CD86 and CD83 expression. Immature DC stimulated to mature with rhsp70 show an enhanced ability to present tyrosinase peptide to specific CTL. Mature DC did not bind rhsp70, suggesting a down-regulation in the expression of its receptor. When rhsp70 was added to monocyte precursors at the same time as GM-CSF and IL-4 it reduced the differentiation of monocytes into DC as shown by a decrease in the level of CD40, CD83, CD86 and HLA-DR expression and an increase in CD14 expression. The constitutively expressed hsc70 had neither a stimulatory effect on the maturation of immature DC nor did it reduce the differentiation of monocytes into DC. These findings demonstrate the specific ability of rhsp70 to induce the maturation of immature DC. Therefore rhsp70 may be useful for its adjuvant like properties in DC based immunotherapy of certain tumors.
- Published
- 2001
- Full Text
- View/download PDF
72. Non-MHC-restricted CD4+ T lymphocytes are regulated by HLA-Cw7-mediated inhibition.
- Author
-
Falk CS, Nössner E, Frankenberger B, and Schendel DJ
- Subjects
- Antibodies, Blocking pharmacology, Antibodies, Monoclonal pharmacology, CD3 Complex biosynthesis, CD4 Antigens biosynthesis, Cell Line, Clone Cells, Cytotoxicity, Immunologic immunology, Epitopes, T-Lymphocyte immunology, Humans, Immunologic Memory, Immunophenotyping, Immunosuppressive Agents pharmacology, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Lymphocyte Activation, Receptors, Immunologic analysis, Receptors, Immunologic antagonists & inhibitors, Receptors, KIR, Receptors, KIR2DL3, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, HLA-C Antigens physiology, Major Histocompatibility Complex immunology, Receptors, Immunologic immunology, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism
- Abstract
Natural killer cells (NK cells) represent an important component of innate immunity with the capacity to kill many tumor and virus-infected cells. The discovery of several classes of killer cell inhibitory receptors expressed by NK cells that bind specific MHC class I ligands on target cells provides detailed insight into the regulation of NK cells. Inhibitory receptors deliver negative signals following MHC ligand binding that abrogate cytotoxicity and, thus, determine the specificity of NK effector cell function. Here, we describe a novel subset of human memory CD4(+) T lymphocytes that display an NK-like pattern of regulation. These CD4(+) T cells display non-MHC-restricted cytotoxicity that is governed by HLA-Cw7 mediated inhibition. In NK cells, such specificity is associated with expression of the inhibitory receptor p58.2. In contrast, neither p58.2 nor other known inhibitory receptors were detected on these non-MHC-restricted CD4(+) T cells. This suggests that these cells are regulated by a hitherto unknown inhibitory receptor. The finding that interactions with MHC molecules downregulate the function of these CD4(+) T cells suggests that these non-MHC-restricted T cells may function to detect and eliminate cells with aberrant MHC expression.
- Published
- 2000
- Full Text
- View/download PDF
73. Cellular and molecular analyses of major histocompatibility complex (MHC) restricted and non-MHC-restricted effector cells recognizing renal cell carcinomas: problems and perspectives for immunotherapy.
- Author
-
Schendel DJ, Oberneder R, Falk CS, Jantzer P, Kressenstein S, Maget B, Hofstetter A, Riethmüller G, and Nössner E
- Subjects
- Humans, Killer Cells, Lymphokine-Activated immunology, Antigen-Antibody Reactions, Carcinoma, Renal Cell therapy, Immunotherapy, Kidney Neoplasms therapy, Major Histocompatibility Complex immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Renal cell carcinomas belong to the small group of tumors that are able to induce antitumor responses. Here we describe two general types of cytotoxic effector lymphocytes that can eliminate autologous tumor cells and discuss the role that major histocompatibility complex encoded molecules play in governing their specificities. Improved understanding of the cellular and molecular basis of renal cell carcinoma recognition opens new avenues of research with the potential to develop better immunotherapies for patients with metastatic disease.
- Published
- 1997
- Full Text
- View/download PDF
74. The HLA likes and dislikes of allospecific and non-MHC-restricted cytotoxic T lymphocytes.
- Author
-
Nössner E, Falk CS, Jantzer P, Reinhardt C, Steinle A, and Schendel DJ
- Subjects
- Animals, Humans, Major Histocompatibility Complex, HLA-A Antigens immunology, HLA-C Antigens immunology, T-Lymphocytes, Cytotoxic immunology
- Published
- 1996
- Full Text
- View/download PDF
75. Microheterogeneity in HLA-B35 alleles influences peptide-dependent allorecognition by cytotoxic T cells but not binding of a peptide-restricted monoclonal antibody.
- Author
-
Steinle A, Reinhardt C, Nössner E, Uchanska-Ziegler B, Ziegler A, and Schendel DJ
- Subjects
- Amino Acid Sequence, Antibodies, Monoclonal, Base Sequence, Binding, Competitive, Cell Line, Genotype, Humans, Molecular Sequence Data, Peptides immunology, HLA-B35 Antigen immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Strong peptide dependency of HLA-B*3501-specific alloreactive T-cell clones was observed in the recognition of cells bearing closely related B35 variants. The single amino acid exchange in the beta-pleated sheet of B*3503 completely abolished the responses of all clones, whereas an amino acid exchange in the alpha 2 helix of the newest B35 member (B*3508) only altered allorecognition of one T-cell clone, demonstrating the differential impact of these positions on peptide binding to B35 molecules. In contrast to T cells, a mAb (TU165) recognizing the B35 specificity in a peptide-dependent manner bound to the B35 variants irrespective of their sequence heterogeneity. However, quantitative binding differences were detected with cells bearing the same B35 alleles. This is most likely due to variations in the amount of peptide(s) that associates with B35 and forms the ligand seen by this mAb. These results reveal how naturally occurring single amino acid substitutions have led to generation of functionally distinct molecules of another multimember HLA class I cluster.
- Published
- 1993
- Full Text
- View/download PDF
76. Soluble T cell receptor-like properties of an HLA-B35-specific monoclonal antibody (TU165).
- Author
-
Uchańska-Ziegler B, Nössner E, Schenk A, Ziegler A, and Schendel DJ
- Subjects
- Antibody Specificity, Cell Line, Humans, In Vitro Techniques, Mutagenesis, Insertional, Peptides immunology, Antibodies, Monoclonal immunology, HLA-B35 Antigen immunology, Receptors, Antigen, T-Cell immunology
- Abstract
A mouse monoclonal antibody of IgM class (TU165) was produced using Epstein-Barr virus (EBV)-infected mutant cells derived from the human BJAB-B95.8.6 cell line as immunogen. Binding studies with several HLA deletion mutant cell lines indicated that TU165 recognized the HLA-B35 molecule. In a panel of 89 EBV-transformed lymphoblastoid cell lines, all HLA-B35+ cells (n = 24) reacted with TU165 while all but two HLA-B35- lines (n = 65) were unreactive (r = 0.95). Surprisingly, peripheral blood lymphocytes of HLA-B35+ donors were unreactive; however, strong enhancement of TU165 recognition was observed with B cells of one of these individuals after transformation with EBV (B95.8 strain). Transfection of both HLA-B35 and human beta 2-microglobulin genomic DNA into mouse P815 cells led to high expression of HLA-B molecules; yet, expression of the TU165 epitope was not observed. Furthermore, the EBV-negative cell line BJAB as well as the EBV-infected (P3HR1 strain) line BJAB-HR1K were only weakly reactive, whereas the BJAB-B95.8 cell line was strongly positive. These results indicate that EBV-encoded or -controlled peptide(s) must be bound by HLA-B35 antigens to create the epitope which allows efficient binding of TU165.
- Published
- 1993
- Full Text
- View/download PDF
77. Isolation and characterization of a genomic HLA-Cw6 clone.
- Author
-
Steinle A, Nössner E, and Schendel DJ
- Subjects
- Alleles, Base Sequence, Cloning, Molecular, DNA isolation & purification, Humans, Molecular Sequence Data, DNA genetics, HLA-C Antigens chemistry, HLA-C Antigens genetics
- Published
- 1992
- Full Text
- View/download PDF
78. Genomic cloning and expression of HLA-B37 in the mouse mastocytoma cell line P815-HTR.
- Author
-
Nelson PJ, Nössner E, and Schendel DJ
- Subjects
- Animals, Base Sequence, DNA genetics, DNA, Recombinant genetics, Exons, Gene Expression, HLA-B Antigens genetics, HLA-B37 Antigen, Humans, Mast-Cell Sarcoma pathology, Mice, Molecular Sequence Data, Polymerase Chain Reaction, Tumor Cells, Cultured metabolism, HLA-B Antigens biosynthesis, Recombinant Fusion Proteins biosynthesis
- Published
- 1991
- Full Text
- View/download PDF
79. HLA-Cw7-associated restriction fragment length polymorphism detected with an HLA-C locus-specific DNA probe.
- Author
-
Nössner E and Schendel DJ
- Subjects
- Alleles, Cell Line, Transformed, Genes, MHC Class I, Haplotypes, Humans, Polymorphism, Restriction Fragment Length, DNA Probes, HLA-C Antigens genetics
- Published
- 1991
- Full Text
- View/download PDF
80. Molecular understanding and clinical outcomes of CAR T cell therapy in the treatment of urological tumors.
- Author
-
Zhang, Gong, Wang, Yuan, Lu, Shiyang, Ding, Fengzhu, Wang, Xia, Zhu, Chunming, Wang, Yibing, and Wang, Kefeng
- Published
- 2024
- Full Text
- View/download PDF
81. Heat shock proteins and dendritic cells: effects on maturation and antigen presentation
- Author
-
Kuppner, M., Milani, V., Gastpar, R., Noessner, E., Roos, M., and Issels, R.
- Published
- 2001
- Full Text
- View/download PDF
82. Autophagy-dependent regulation of MHC-I molecule presentation.
- Author
-
Gestal-Mato U and Herhaus L
- Subjects
- Humans, Animals, Dendritic Cells immunology, Dendritic Cells metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Endoplasmic Reticulum metabolism, Cross-Priming immunology, Autophagy, Histocompatibility Antigens Class I metabolism, Histocompatibility Antigens Class I immunology, Antigen Presentation immunology
- Abstract
The major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I-restricted CD8+ T lymphocytes to elicit an effective immune response. The conventional antigen-processing pathway for MHC-I presentation depends on proteasome-mediated peptide generation and peptide loading in the endoplasmic reticulum by members of the peptide loading complex. Recent discoveries in this field highlight the role of alternative MHC-I peptide loading and presentation pathways, one of them being autophagy. Autophagy is a cell-intrinsic degradative pathway that ensures cellular homoeostasis and plays critical roles in cellular immunity. In this review article, we discuss the role of autophagy in MHC class I-restricted antigen presentation, elucidating new findings on the crosstalk of autophagy and ER-mediated MHC-I peptide presentation, dendritic cell-mediated cross-presentation and also mechanisms governing immune evasion. A detailed molecular understanding of the key drivers of autophagy-mediated MHC-I modulation holds promising targets to devise effective measures to improve T cell immunotherapies., (© 2023 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
83. Virus-specific T-cells from third party or transplant donors for treatment of EBV lymphoproliferative diseases arising post hematopoietic cell or solid organ transplantation.
- Author
-
O'Reilly, Richard J., Prockop, Susan, and Oved, Joseph H.
- Subjects
EPSTEIN-Barr virus diseases ,LYMPHOPROLIFERATIVE disorders ,T cells ,TRANSPLANTATION of organs, tissues, etc. ,RITUXIMAB ,BK virus - Abstract
EBV
+ lymphomas constitute a significant cause of morbidity and mortality in recipients of allogeneic hematopoietic cell (HCT) and solid organ transplants (SOT). Phase I and II trials have shown that in HCT recipients, adoptive transfer of EBV-specific T-cells from the HCT donor can safely induce durable remissions of EBV+ lymphomas including 70->90% of patients who have failed to respond to treatment with Rituximab. More recently, EBV-specific T-cells generated from allogeneic 3rd party donors have also been shown to induce durable remission of EBV+ lymphomas in Rituximab refractory HCT and SOT recipients. In this review, we compare results of phase I and II trials of 3rd party and donor derived EBVspecific T-cells. We focus on the attributes and limitations of each product in terms of access, safety, responses achieved and durability. The limited data available regarding donor and host factors contributing to T cell persistence is also described. We examine factors contributing to treatment failures and approaches to prevent or salvage relapse. Lastly, we summarize strategies to further improve results for virus-specific immunotherapies for post-transplant EBV lymphomas. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
84. A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines.
- Author
-
Patel, Dixita M., Mateen, Ruba, Qaddour, Noor, Carrillo, Alessandra, Verschraegen, Claire, Yang, Yuanquan, Li, Zihai, Sundi, Debasish, Mortazavi, Amir, and Collier, Katharine A.
- Subjects
THERAPEUTIC use of monoclonal antibodies ,THERAPEUTIC use of antineoplastic agents ,BLADDER tumors ,DRUG approval ,CLINICAL trials ,IMMUNE checkpoint inhibitors ,CELLULAR therapy ,CANCER chemotherapy ,METASTASIS ,INVESTIGATIONAL drugs ,TRANSITIONAL cell carcinoma ,TREATMENT effectiveness ,PROTEIN-tyrosine kinase inhibitors ,GEMCITABINE ,NIVOLUMAB ,CISPLATIN ,CANCER vaccines ,IMMUNOTHERAPY ,OVERALL survival - Abstract
Simple Summary: Metastatic urothelial carcinoma is sensitive to immunomodulation. Immune checkpoint inhibitors (ICIs) have been FDA approved for use as single agents to treat locally advanced or metastatic urothelial carcinoma (mUC) since 2016. Immunotherapy has a lower incidence of side effects and longer durability of response compared to chemotherapy. Most recently, both the first-line combinations of pembrolizumab plus enfortumab vedotin and of nivolumab plus gemcitabine plus cisplatin showed significant overall survival benefit over prior standard-of-care chemotherapy and will be the fifth and sixth new drug regimens approved for mUC in the past four years. Treatment options for mUC are expected to continue to rapidly evolve. Here, we summarize clinical trials of immunotherapy that have led to the current standard of care for mUC, then review clinical trials testing novel immunotherapeutic approaches. A comprehensive understanding of current clinical trials will enable anticipation of upcoming developments and future research directions for mUC. Urothelial cancer is an immune-responsive cancer, but only a subset of patients benefits from immune checkpoint inhibition. Currently, single-agent immune checkpoint inhibitors (ICIs) and the combination of pembrolizumab with the antibody–drug conjugate enfortumab vedotin are approved to treat patients with metastatic UC (mUC). Approval of first-line nivolumab in combination with gemcitabine and cisplatin is expected imminently. Many treatment approaches are being investigated to better harness the immune system to fight mUC. In this review, we summarize the landmark clinical trials of ICIs that led to their incorporation into the current standard of care for mUC. We further discuss recent and ongoing clinical trials in mUC, which are investigating ICIs in combination with other agents, including chemotherapy, antibody–drug conjugates, tyrosine kinase inhibitors, and novel antibodies. Lastly, we review novel approaches utilizing bispecific antibodies, cellular therapies, and vaccines. The landscape of immunotherapy for mUC is rapidly evolving and will hopefully lead to better outcomes for patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
85. CD44v6, STn & O-GD2: promising tumor associated antigens paving the way for new targeted cancer therapies.
- Author
-
Lodewijk, Iris, Dueñas, Marta, Paramio, Jesus M., and Rubio, Carolina
- Subjects
TUMOR antigens ,CANCER treatment ,CHIMERIC antigen receptors ,RECOMBINANT antibodies ,GENE expression - Abstract
Targeted therapies are the state of the art in oncology today, and every year new Tumor-associated antigens (TAAs) are developed for preclinical research and clinical trials, but few of them really change the therapeutic scenario. Difficulties, either to find antigens that are solely expressed in tumors or the generation of good binders to these antigens, represent a major bottleneck. Specialized cellular mechanisms, such as differential splicing and glycosylation processes, are a good source of neo-antigen expression. Changes in these processes generate surface proteins that, instead of showing decreased or increased antigen expression driven by enhanced mRNA processing, are aberrant in nature and therefore more specific targets to elicit a precise anti-tumor therapy. Here, we present promising TAAs demonstrated to be potential targets for cancer monitoring, targeted therapy and the generation of new immunotherapy tools, such as recombinant antibodies and chimeric antigen receptor (CAR) T cell (CAR-T) or Chimeric Antigen Receptor-Engineered Natural Killer (CAR-NK) for specific tumor killing, in a wide variety of tumor types. Specifically, this review is a detailed update on TAAs CD44v6, STn and O-GD2, describing their origin as well as their current and potential use as disease biomarker and therapeutic target in a diversity of tumor types. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
86. The dysfunction of CD8 + T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis.
- Author
-
Huang ZX, Lin DC, Zhang HY, Yang MJ, Chen JH, Ding XY, Dai SJ, Hong YH, Liang GS, Li QY, and Chen QH
- Subjects
- Female, Humans, Animals, Mice, Programmed Cell Death 1 Receptor metabolism, Endometrium immunology, Endometrium pathology, Disease Models, Animal, Signal Transduction, Mice, Nude, Adult, CDC2 Protein Kinase metabolism, Coculture Techniques, Cytokines metabolism, Endometriosis immunology, Endometriosis pathology, Endometriosis metabolism, CD8-Positive T-Lymphocytes immunology, Stromal Cells immunology, Stromal Cells metabolism, STAT1 Transcription Factor metabolism
- Abstract
Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8
+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+ , was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis., (© 2024 John Wiley & Sons Ltd.)- Published
- 2024
- Full Text
- View/download PDF
87. Understanding endometriosis from an immunomicroenvironmental perspective.
- Author
-
Dian Fan, Xu Wang, Zhixian Shi, Yuting Jiang, Bohao Zheng, Lian Xu, and Shengtao Zhou
- Published
- 2023
- Full Text
- View/download PDF
88. CACYBP knockdown inhibits progression of prostate cancer via p53.
- Author
-
Li, Qiang, Liu, Zhili, Ma, Luping, Yin, Weiqi, and Zhang, Kan
- Subjects
PROSTATE cancer ,CANCER invasiveness ,CELL cycle ,CELL migration ,TUMOR growth ,ANDROGEN receptors - Abstract
Purpose: Prostate cancer (PC) is one of the most common malignant tumors of genitourinary system in men. CACYCLIN binding protein (CACYBP) is involved in the progression of a variety of cancers. The aim of this study was to explore the expression and functional role of CACYBP in PC. Methods: The expression of CACYBP in PC was evaluated by immunohistochemical (IHC) staining and qRT-PCR. Subsequently, we established lentivirus-mediated CACYBP knockdown in PC cell lines. The biological roles of CACYBP on proliferation, apoptosis, cycle distribution, migration and tumor formation of PC were investigated by Celigo cell counting assay, flow cytometry, transwell assay, wound-healing assay and mice xenograft models, respectively. Results: CACYBP was highly expressed in PC and was positively correlated with the pathological grade of PC patients. Knockdown of CACYBP inhibited proliferation, enhanced apoptosis, arrested cell cycle in G2 and suppressed migration of PC cell lines in vitro. In addition, CACYBP knockdown weakened the tumor growth of PC in vivo. Moreover, addition of p53 inhibitor could effectively alleviate the inhibitory effect of CACYBP knockdown on cell activity. Conclusion: This study revealed that knockdown of CACYBP inhibited the proliferation, migration and tumorigenicity of PC, which may serve as a potential therapeutic target for the treatment of PC. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
89. Cell Surface B2m-Free Human Leukocyte Antigen (HLA) Monomers and Dimers: Are They Neo-HLA Class and Proto-HLA?
- Author
-
Ravindranath, Mepur H., Ravindranath, Narendranath M., Selvan, Senthamil R., Hilali, Fatiha El, Amato-Menker, Carly J., and Filippone, Edward J.
- Subjects
HLA histocompatibility antigens ,LUNGS ,MONOMERS ,BREAST ,DIMERS ,AMINO acid sequence ,SEMINAL vesicles - Abstract
Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell surface without peptides as B2m-free HC monomers (Face-2), B2m-free HC homodimers (Face 3), and B2m-free HC heterodimers (Face-4). The transport of these HLA variants from ER to the cell surface was confirmed by antiviral antibiotics that arrest the release of newly synthesized proteins from the ER. Face-2 occurs at low levels on the normal cell surface of the lung, bronchi, epidermis, esophagus, breast, stomach, ilium, colorectum, gall bladder, urinary bladder, seminal vesicles ovarian epithelia, endometrium, thymus, spleen, and lymphocytes. They are upregulated on immune cells upon activation by proinflammatory cytokines, anti-CD3 antibodies, antibiotics (e.g., ionomycin), phytohemagglutinin, retinoic acid, and phorbol myristate acetate. Their density on the cell surface remains high as long as the cells remain in an activated state. After activation-induced upregulation, the Face-2 molecules undergo homo- and hetero-dimerization (Face-3 and Face-4). Alterations in the redox environment promote dimerization. Heterodimerization can occur among and between the alleles of different haplotypes. The glycosylation of these variants differ from that of Face-1, and they may occur with bound exogenous peptides. Spontaneous arthritis occurs in HLA-B27+ mice lacking B2m (HLA-B27+ B2m−/−) but not in HLA-B27+ B2m+/− mice. The mice with HLA-B27 in Face-2 spontaneous configuration develop symptoms such as changes in nails and joints, hair loss, and swelling in paws, leading to ankyloses. Anti-HC-specific mAbs delay disease development. Some HLA-I polyreactive mAbs (MEM series) used for immunostaining confirm the existence of B2m-free variants in several cancer cells. The upregulation of Face-2 in human cancers occurs concomitantly with the downregulation of intact HLAs (Face-1). The HLA monomeric and dimeric variants interact with inhibitory and activating ligands (e.g., KIR), growth factors, cytokines, and neurotransmitters. Similarities in the amino acid sequences of the HLA-I variants and HLA-II β-chain suggest that Face-2 could be the progenitor of both HLA classes. These findings may support the recognition of these variants as a neo-HLA class and proto-HLA. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
90. The significance of immune microenvironment in patients with endometriosis.
- Author
-
PĂVĂLEANU, IOANA, BALAN, RALUCA ANCA, GRIGORAŞ, ADRIANA, BALAN, TEODORA ANA, and AMĂLINEI, CORNELIA
- Published
- 2023
- Full Text
- View/download PDF
91. Analysis of HLA-B35 variants and B35 haplotypes by isoelectric focusing and Southern blot analysis.
- Author
-
Lederer E, Nössner E, Wank R, and Schendel DJ
- Subjects
- Blotting, Southern, DNA Probes, Genetic Linkage, Humans, Isoelectric Focusing, Polymorphism, Restriction Fragment Length, Genetic Variation, HLA-B Antigens genetics, Haplotypes
- Published
- 1989
- Full Text
- View/download PDF
92. Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer.
- Author
-
Raftery, Martin J., Franzén, Alexander Sebastian, Radecke, Clarissa, Boulifa, Abdelhadi, Schönrich, Günther, Stintzing, Sebastian, Blohmer, Jens-Uwe, and Pecher, Gabriele
- Subjects
TRIPLE-negative breast cancer ,CHIMERIC antigen receptors ,PROGRAMMED cell death 1 receptors - Abstract
There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). Chimeric antigen receptor (CAR) natural killer (NK) cells are a promising alternative to CAR-T cell therapy for cancer. A search for a suitable target in TNBC identified CD44v6, an adhesion molecule expressed in lymphomas, leukemias and solid tumors that is implicated in tumorigenesis and metastases. We have developed a next-generation CAR targeting CD44v6 that incorporates IL-15 superagonist and checkpoint inhibitor molecules. We could show that CD44v6 CAR-NK cells demonstrated effective cytotoxicity against TNBC in 3D spheroid models. The IL-15 superagonist was specifically released upon recognition of CD44v6 on TNBC and contributed to the cytotoxic attack. PD1 ligands are upregulated in TNBC and contribute to the immunosuppressive tumor microenvironment (TME). Competitive inhibition of PD1 neutralized inhibition by PD1 ligands expressed on TNBC. In total, CD44v6 CAR-NK cells are resistant to TME immunosuppression and offer a new therapeutic option for the treatment of BC, including TNBC. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
93. Demethylating therapy increases cytotoxicity of CD44v6 CAR-T cells against acute myeloid leukemia.
- Author
-
Ling Tang, Yingjie Kong, Haobing Wang, Ping Zou, Ting Sun, Ying Liu, Juan Zhang, Na Jin, Hanwen Mao, Xiaojian Zhu, Jue Wang, Fankai Meng, and Yong You
- Subjects
ACUTE myeloid leukemia ,DECITABINE ,AZACITIDINE ,GENE expression profiling ,T-cell exhaustion ,CHIMERIC antigen receptors ,PROTEIN-tyrosine kinases - Abstract
Background: CD44v6 chimeric antigen receptor T (CD44v6 CAR-T) cells demonstrate strong anti-tumor ability and safety in acute myeloid leukemia (AML). However, the expression of CD44v6 on T cells leads to transient fratricide and exhaustion of CD44v6 CAR-T cells, which affect the application of CD44v6 CAR-T. The exhaustion and function of T cells and CD44v6 expression of AML cells are associated with DNA methylation. Hypomethylating agents (HAMs) decitabine (Dec) and azacitidine (Aza) have been widely used to treat AML. Therefore, there may be synergy between CD44v6 CAR-T cells and HAMs in the treatment of AML. Methods: CD44v6 CAR-T cells pretreated with Dec or Aza were co-cultured with CD44v6+ AML cells. Dec or aza pretreated AML cells were co-cultured with CD44v6 CAR-T cells. The cytotoxicity, exhaustion, differentiation and transduction efficiency of CAR-T cells, and CD44v6 expression and apoptosis in AML cells were detected by flow cytometry. The subcutaneous tumor models were used to evaluate the anti-tumor effect of CD44v6 CAR-T cells combined with Dec in vivo. The effects of Dec or Aza on gene expression profile of CD44v6 CAR-T cells were analyzed by RNA-seq. Results: Our results revealed that Dec and Aza improved the function of CD44v6 CAR-T cells through increasing the absolute output of CAR+ cells and persistence, promoting activation and memory phenotype of CD44v6 CAR-T cells, and Dec had a more pronounced effect. Dec and Aza promoted the apoptosis of AML cells, particularly with DNA methyltransferase 3A (DNMT3A) mutation. Dec and Aza also enhanced the CD44v6 CAR-T response to AML by upregulating CD44v6 expression of AML cells regardless of FMS-like tyrosine kinase 3 (FLT3) or DNMT3A mutations. The combination of Dec or Aza pretreated CD44v6 CAR-T with pretreated AML cells demonstrated the most potent antitumor ability against AML. Conclusion: Dec or Aza in combination with CD44v6 CAR-T cells is a promising combination therapy for AML patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
94. Epigenetic modifications in esophageal cancer: An evolving biomarker.
- Author
-
Wen-Jian Liu, Yuan Zhao, Xu Chen, Man-Li Miao, and Ren-Quan Zhang
- Subjects
ESOPHAGEAL cancer ,CHROMATIN-remodeling complexes ,RNA regulation ,HISTONES ,EPIGENETICS ,TUMOR markers ,NON-coding RNA - Abstract
Esophageal cancer is a widespread cancer of the digestive system that has two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). In the diverse range of cancer therapy schemes, the side effects of conventional treatments remain an urgent challenge to be addressed. Therefore, the pursuit of novel drugs with multiple targets, good efficacy, low side effects, and low cost has become a hot research topic in anticancer therapy. Based on this, epigenetics offers an attractive target for the treatment of esophageal cancer, where major mechanisms such as DNA methylation, histone modifications, noncoding RNA regulation, chromatin remodelling and nucleosome localization offer new opportunities for the prevention and treatment of esophageal cancer. Recently, research on epigenetics has remained at a high level of enthusiasm, focusing mainly on translating the basic research into the clinical setting and transforming epigenetic alterations into targets for cancer screening and detection in the clinic. With the increasing emergence of tumour epigenetic markers and antitumor epigenetic drugs, there are also more possibilities for anti-esophageal cancer treatment. This paper focuses on esophageal cancer and epigenetic modifications, with the aim of unravelling the close link between them to facilitate precise and personalized treatment of esophageal cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
95. Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.
- Author
-
Gaál, Zsuzsanna
- Subjects
CHILDHOOD cancer ,HYDROXAMIC acids ,EPIGENETICS ,HISTONE deacetylase inhibitors ,HISTONES ,SARCOMA ,KIDNEY tumors ,CD19 antigen - Abstract
Over the past two decades, novel hallmarks of cancer have been described, including the altered epigenetic landscape of malignant diseases. In addition to the methylation and hyd-roxymethylation of DNA, numerous novel forms of histone modifications and nucleosome remodeling have been discovered, giving rise to a wide variety of targeted therapeutic interventions. DNA hypomethylating drugs, histone deacetylase inhibitors and agents targeting histone methylation machinery are of distinguished clinical significance. The major focus of this review is placed on targeted epigenetic interventions in the most common pediatric malignancies, including acute leukemias, brain and kidney tumors, neuroblastoma and soft tissue sarcomas. Upcoming novel challenges include specificity and potential undesirable side effects. Different epigenetic patterns of pediatric and adult cancers should be noted. Biological significance of epigenetic alterations highly depends on the tissue microenvironment and widespread interactions. An individualized treatment approach requires detailed genetic, epigenetic and metabolomic evaluation of cancer. Advances in molecular technologies and clinical translation may contribute to the development of novel pediatric anticancer treatment strategies, aiming for improved survival and better patient quality of life. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
96. Role of Epitranscriptomic and Epigenetic Modifications during the Lytic and Latent Phases of Herpesvirus Infections.
- Author
-
Soto, Abel A., Ortiz, Gerardo, Contreras, Sofía, Soto-Rifo, Ricardo, and González, Pablo A.
- Abstract
Herpesviruses are double-stranded DNA viruses occurring at a high prevalence in the human population and are responsible for a wide array of clinical manifestations and diseases, from mild to severe. These viruses are classified in three subfamilies (Alpha-, Beta- and Gammaherpesvirinae), with eight members currently known to infect humans. Importantly, all herpesviruses can establish lifelong latent infections with symptomatic or asymptomatic lytic reactivations. Accumulating evidence suggest that chemical modifications of viral RNA and DNA during the lytic and latent phases of the infections caused by these viruses, are likely to play relevant roles in key aspects of the life cycle of these viruses by modulating and regulating their replication, establishment of latency and evasion of the host antiviral response. Here, we review and discuss current evidence regarding epitranscriptomic and epigenetic modifications of herpesviruses and how these can influence their life cycles. While epitranscriptomic modifications such as m
6 A are the most studied to date and relate to positive effects over the replication of herpesviruses, epigenetic modifications of the viral genome are generally associated with defense mechanisms of the host cells to suppress viral gene transcription. However, herpesviruses can modulate these modifications to their own benefit to persist in the host, undergo latency and sporadically reactivate. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
97. CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future.
- Author
-
Zhengchao Zhang, Dong Li, Heng Yun, Wei Liu, Keqiang Chai, Jie Tong, Tongwei Zeng, Zhenghua Gao, and Yongqiang Xie
- Subjects
TUMORS ,ORGANS (Anatomy) ,ANTINEOPLASTIC agents ,TUMOR treatment ,DESMOID tumors ,RENAL cancer - Abstract
In recent years, with the breakthrough of CAR-T cells in the treatment of hematological tumors, they are increasingly being used to treat solid tumors, including urologic neoplasms. There are many relatively specific targets for urologic neoplasms, especially prostate cancer. Besides, urologic neoplasms tend to progress more slowly than tumors in other organs of the body, providing ample time for CAR-T cell application. Therefore, CAR-T cells technology has inherent advantages in urologic neoplasms. CAR-T cells in the treatment of urologic neoplasms have been extensively studied and preliminary achievements have been made. However, no breakthrough has been made due to the problems of targeting extra-tumor cytotoxicity and poor anti-tumor activity. we systematacially summarized the research actuality of CAR-T cells in urologic neoplasms, discussed the potential value and difficulties of the research. The application of CAR-T cells in the treatment of urologic neoplasms requires improvement of function through screening for better targets, modification of CAR structures, or in combination with other antitumor approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
98. Reconstitution of EBV-directed T cell immunity by adoptive transfer of peptide-stimulated T cells in a patient after allogeneic stem cell transplantation for AITL.
- Author
-
Lammoglia Cobo, María Fernanda, Ritter, Julia, Gary, Regina, Seitz, Volkhard, Mautner, Josef, Aigner, Michael, Völkl, Simon, Schaffer, Stefanie, Moi, Stephanie, Seegebarth, Anke, Bruns, Heiko, Rösler, Wolf, Amann, Kerstin, Büttner-Herold, Maike, Hennig, Steffen, Mackensen, Andreas, Hummel, Michael, Moosmann, Andreas, and Gerbitz, Armin
- Subjects
STEM cell transplantation ,T cells ,T cell receptors ,T-cell lymphoma ,CELL populations ,EPSTEIN-Barr virus - Abstract
Reconstitution of the T cell repertoire after allogeneic stem cell transplantation is a long and often incomplete process. As a result, reactivation of Epstein-Barr virus (EBV) is a frequent complication that may be treated by adoptive transfer of donor-derived EBV-specific T cells. We generated donor-derived EBV-specific T cells by stimulation with peptides representing defined epitopes covering multiple HLA restrictions. T cells were adoptively transferred to a patient who had developed persisting high titers of EBV after allogeneic stem cell transplantation for angioimmunoblastic T-cell lymphoma (AITL). T cell receptor beta (TCRβ) deep sequencing showed that the T cell repertoire of the patient early after transplantation (day 60) was strongly reduced and only very low numbers of EBV-specific T cells were detectable. Manufacturing and in vitro expansion of donor-derived EBV-specific T cells resulted in enrichment of EBV epitope-specific, HLA-restricted T cells. Monitoring of T cell clonotypes at a molecular level after adoptive transfer revealed that the dominant TCR sequences from peptide-stimulated T cells persisted long-term and established an EBV-specific TCR clonotype repertoire in the host, with many of the EBV-specific TCRs present in the donor. This reconstituted repertoire was associated with immunological control of EBV and with lack of further AITL relapse. Author summary: A characteristic feature of all herpesviruses is their persistence in the host's body after primary infection. Hence, the host's immune system is confronted with the problem to control these viruses life-long. When the immune system is severely compromised, for example after stem cell transplantation from a foreign (allogeneic) donor, these viruses can reappear, as they persist in the host's body life-long after primary infection. Epstein-Barr virus (EBV) is a herpesvirus that can cause life-threatening complications after stem cell transplantation and only reinforcement of the host's immune system can reestablish control over the virus. Here we show that ex vivo manufactured EBV-specific T cells can reestablish long-term control of EBV and that these cells persist in the host's body over months. These results give us a better understanding of viral immune reconstitution post-transplant and of clinically-relevant T cell populations against EBV. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
99. Extracellular HSPs: The Potential Target for Human Disease Therapy.
- Author
-
Li, Dong-Yi, Liang, Shan, Wen, Jun-Hao, Tang, Ji-Xin, Deng, Shou-Long, and Liu, Yi-Xun
- Subjects
HEAT shock proteins ,EXTRACELLULAR matrix ,CELL compartmentation ,MOLECULAR chaperones ,IMMUNOREGULATION ,NEURODEGENERATION ,IMMUNE response ,DISEASE progression - Abstract
Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses. Recent studies have demonstrated that extracellular HSPs (eHSPs) were involved in many human diseases, such as cancers, neurodegenerative diseases, and kidney diseases, which are all diseases that are closely linked to inflammation and immunity. In this review, we describe the types of eHSPs, discuss the mechanisms of eHSPs secretion, and then highlight their functions in the modulation of inflammation and immune responses. Finally, we take cancer as an example and discuss the possibility of targeting eHSPs for human disease therapy. A broader understanding of the function of eHSPs in development and progression of human disease is essential for developing new strategies to treat many human diseases that are critically related to inflammation and immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
100. Genome Assembly and Genome Annotation of Leishmania martiniquensis Isolated from a Leishmaniasis Patient in Thailand.
- Author
-
Anuntakarun, Songtham, Phumee, Atchara, Sawaswong, Vorthon, Praianantathavorn, Kesmanee, Poomipak, Witthaya, Jitvaropas, Rungrat, Siriyasatien, Padet, and Payungporn, Sunchai
- Subjects
LEISHMANIASIS ,LEISHMANIA ,SUPEROXIDE dismutase ,GENOMES ,PARASITIC diseases ,GENOMICS ,ANNOTATIONS - Abstract
Leishmaniasis is a parasitic disease caused by Leishmania spp. with worldwide distribution. Autochthonous leishmaniasis has been reported to result from the infection by Leishmania martiniquensis in Thailand. This species was isolated in culture and subjected to high-throughput whole-genome sequencing. A total of 30.8 Mb in 36 chromosomes of the whole genome was assembled, annotated, and characterized. The L. martiniquensis under study was shown to segregate into the same clade and thus closely related to the previously identified L. martiniquensis (LU_Lmar_1.0), as determined by phylogenetic analysis of their genomic sequences along with those of representative kinetoplastid species. The total number of open reading frames genomewide predicts 8,209 protein-coding genes, of which 359 are putative virulence factors, including two previously known, e.g., cysteine proteinase C and superoxide dismutase B1. The results obtained from this study will be useful for further annotation and comparison with other Leishmania martiniquensis in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.