دورية أكاديمية
Reinforcement of cell-mediated immunity driven by tumor-associated Epstein-Barr virus (EBV)-specific T cells during targeted B-cell therapy with rituximab.
| العنوان: | Reinforcement of cell-mediated immunity driven by tumor-associated Epstein-Barr virus (EBV)-specific T cells during targeted B-cell therapy with rituximab. |
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| المؤلفون: | Tischer-Zimmermann, Sabine, Bonifacius, Agnes, Santamorena, Maria Michela, Mausberg, Philip, Stoll, Sven, Döring, Marius, Kalinke, Ulrich, Blasczyk, Rainer, Maecker-Kolhoff, Britta, Eiz-Vesper, Britta |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | article, ddc:610, Humans, Herpesvirus 4, Human, Epstein-Barr Virus Infections, Neoplasms, Antigens, Immunity, Cellular, Cell- and Tissue-Based Therapy, Rituximab, epstein-barr virus (EBV), Cross-presentation, Cytotoxic T Cells (Ctl), Ebv+ B-Lcls |
| الوصف: | Introduction In immunocompromised patients, Epstein-Barr virus (EBV) infection or reactivation is associated with increased morbidity and mortality, including the development of B-cell lymphomas. The first-line treatment consists of reduction of immunosuppression and administration of rituximab (anti-CD20 antibody). Furthermore, the presence of EBV-specific T cells against latent EBV proteins is crucial for the control of EBV-associated diseases. Therefore, in addition to effective treatment strategies, appropriate monitoring of T cells of high-risk patients is of great importance for improving clinical outcome. In this study, we hypothesized that rituximab-mediated lysis of malignant EBV-infected B cells leads to the release and presentation of EBV-associated antigens and results in an augmentation of EBV-specific effector memory T-cell responses. Methods EBV-infected B lymphoblastoid cell lines (B-LCLs) were used as a model for EBV-associated lymphomas, which are capable of expressing latency stage II and III EBV proteins present in all known EBV-positive malignant cells. Rituximab was administered to obtain cell lysates containing EBV antigens (ACEBV). Efficiency of cross-presentation of EBV-antigen by B-LCLs compared to cross-presentation by professional antigen presenting cells (APCs) such as dendritic cells (DCs) and B cells was investigated by in vitro T-cell immunoassays. Deep T-cell profiling of the tumor-reactive EBV-specific T cells in terms of activation, exhaustion, target cell killing, and cytokine profile was performed, assessing the expression of T-cell differentiation and activation markers as well as regulatory and cytotoxic molecules by interferon-γ (IFN-γ) EliSpot assay, multicolor flow cytometry, and multiplex analyses. Results By inhibiting parts of the cross-presentation pathway, B-LCLs were shown to cross-present obtained exogenous ACEBV-derived antigens mainly through major histocompatibility complex (MHC) class I molecules. This mechanism is comparable to that for DCs and B cells and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | Frontiers in immunology -- Front Immunol -- http://www.bibliothek.uni-regensburg.de/ezeit/?2606827Test -- http://www.frontiersin.org/immunologyTest -- https://www.ncbi.nlm.nih.gov/pmc/journals/1754Test/ -- 1664-3224; https://doi.org/10.3389/fimmu.2023.878953Test; https://mhh-publikationsserver.gbv.de/receive/mhh_mods_00002488Test; https://mhh-publikationsserver.gbv.de/servlets/MCRFileNodeServlet/mhh_derivate_00002383/fimmu-14-878953_a.pdfTest; https://europepmc.org/articles/PMC10079996Test |
| DOI: | 10.3389/fimmu.2023.878953 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2023.878953Test https://mhh-publikationsserver.gbv.de/receive/mhh_mods_00002488Test https://mhh-publikationsserver.gbv.de/servlets/MCRFileNodeServlet/mhh_derivate_00002383/fimmu-14-878953_a.pdfTest https://europepmc.org/articles/PMC10079996Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ ; public ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.AF7544A9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2023.878953 |
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