دورية أكاديمية
Identification of non-mutated neoantigens presented by TAP-deficient tumors.
العنوان: | Identification of non-mutated neoantigens presented by TAP-deficient tumors. |
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المؤلفون: | Marijt KA; Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands., Blijleven L; Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands., Verdegaal EME; Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands., Kester MG; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Kowalewski DJ; Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.; German Cancer Consortium, German Cancer Research Center, Tübingen, Germany., Rammensee HG; Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.; German Cancer Consortium, German Cancer Research Center, Tübingen, Germany., Stevanović S; Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.; German Cancer Consortium, German Cancer Research Center, Tübingen, Germany., Heemskerk MHM; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., van der Burg SH; Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands., van Hall T; Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands T.van_Hall@lumc.nl. |
المصدر: | The Journal of experimental medicine [J Exp Med] 2018 Sep 03; Vol. 215 (9), pp. 2325-2337. Date of Electronic Publication: 2018 Aug 16. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: New York, NY : Rockefeller University Press |
مواضيع طبية MeSH: | Antigen Presentation* , Tumor Escape*, ATP-Binding Cassette Transporters/*deficiency , Antigens, Neoplasm/*immunology , CD8-Positive T-Lymphocytes/*immunology , HLA-A2 Antigen/*immunology , LDL-Receptor Related Protein-Associated Protein/*immunology , Neoplasm Proteins/*immunology , Neoplasms/*immunology, ATP-Binding Cassette Transporters/immunology ; CD8-Positive T-Lymphocytes/pathology ; Female ; Humans ; Male ; Neoplasms/pathology ; Tumor Cells, Cultured |
مستخلص: | Most T cell-based immunotherapies of cancer depend on intact antigen presentation by HLA class I molecules (HLA-I). However, defects in the antigen-processing machinery can cause downregulation of HLA-I, rendering tumor cells resistant to CD8 + T cells. Previously, we demonstrated that a unique category of cancer antigens is selectively presented by tumor cells deficient for the peptide transporter TAP, enabling a specific attack of such tumors without causing immunopathology in mouse models. With a novel combinatorial screening approach, we now identify 16 antigens of this category in humans. These HLA-A*02:01 presented peptides do not derive from the mutanome of cancers, but are of "self" origin and therefore constitute universal neoantigens. Indeed, CD8 + T cells specific for the leader peptide of the ubiquitously expressed LRPAP1 protein recognized TAP-deficient, HLA-I low lymphomas, melanomas, and renal and colon carcinomas, but not healthy counterparts. In contrast to personalized mutanome-targeted therapies, these conserved neoantigens and their cognate receptors can be exploited for immune-escaped cancers across diverse histological origins. (© 2018 Marijt et al.) |
التعليقات: | Comment in: J Exp Med. 2018 Sep 3;215(9):2233-2234. (PMID: 30131364) |
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سلسلة جزيئية: | SWISSPROT Q9Y282; Q9C0H2; P01591; P15289; Q9BXX0; O60613; P29459; P00739; Q6MZW2; P40259; Q9Y5G7; Q9NUB4; P02743 |
المشرفين على المادة: | 0 (ATP-Binding Cassette Transporters) 0 (Antigens, Neoplasm) 0 (HLA-A*02:01 antigen) 0 (HLA-A2 Antigen) 0 (LDL-Receptor Related Protein-Associated Protein) 0 (Neoplasm Proteins) 0 (transporter associated with antigen processing (TAP)) |
تواريخ الأحداث: | Date Created: 20180818 Date Completed: 20190904 Latest Revision: 20210105 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC6122969 |
DOI: | 10.1084/jem.20180577 |
PMID: | 30115740 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1540-9538 |
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DOI: | 10.1084/jem.20180577 |