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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Rammensee, Hans-georg Schuster, Heiko Stickel, Juliane Sarah Berlin, Claudia Kanz, Lothar Stevanovic, Stefan Kowalewski, Daniel J. Salih, Helmut R. Backert, Linus Kahn, Stefan |
| Description | Author Affiliation: Kowalewski DJ ( Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen 72076, Germany); Schuster H ( Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen 72076, Germany); Backert L ( Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen 72076, Germany); Berlin C ( Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen 72076, Germany); Kahn S ( Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen 72076, Germany); Kanz L ( Department of Hematology and Oncology, University of Tübingen, Tübingen 72076, Germany); Salih HR ( Department of Hematology and Oncology, University of Tübingen, Tübingen 72076, Germany); Rammensee HG ( Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen 72076, Germany); Stevanovic S ( Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen 72076, Germany); Stickel JS ( Department of Hematology and Oncology, University of Tübingen, Tübingen 72076, Germany); |
| Abstract | The breakthrough development of clinically effective immune checkpoint inhibitors illustrates the potential of T-cell-based immunotherapy to effectively treat malignancies. A remaining challenge is to increase and guide the specificities of anticancer immune responses, e.g., by therapeutic vaccination or by adoptive T-cell transfer. By analyzing the landscape of naturally presented HLA class I and II ligands of primary chronic lymphocytic leukemia (CLL), we delineated a novel category of tumor-associated T-cell antigens based on their exclusive and frequent representation in the HLA ligandome of leukemic cells. These antigens were validated across different stages and mutational subtypes of CLL and found to be robustly represented in HLA ligandomes of patients undergoing standard chemo-/immunotherapy. We demonstrate specific immune recognition of these antigens exclusively in CLL patients, with the frequencies of representation in CLL ligandomes correlating with the frequencies of immune recognition by patient T cells. Moreover, retrospective survival analysis revealed survival benefits for patients displaying immune responses to these antigens. These results directly imply these nonmutant self-peptides as pathophysiologically relevant tumor antigens and encourages their implementation for cancer immunotherapy. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | HLA Antigens Metabolism Immunotherapy Leukemia, Lymphocytic, Chronic, B-Cell Immunology Therapy Amino Acid Sequence Antigen Presentation Antigens, Differentiation, T-Lymphocyte Antigens, Neoplasm CD4-Positive T-Lymphocytes Cancer Vaccines Genetics Immunity, Innate Ligands Molecular Sequence Data Vaccines, Subunit Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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