دورية أكاديمية
Clonal Abundance of Tumor-Specific CD4(+) T Cells Potentiates Efficacy and Alters Susceptibility to Exhaustion.
العنوان: | Clonal Abundance of Tumor-Specific CD4(+) T Cells Potentiates Efficacy and Alters Susceptibility to Exhaustion. |
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المؤلفون: | Malandro N; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA., Budhu S; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Kuhn NF; Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Liu C; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Murphy JT; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA., Cortez C; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Zhong H; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Yang X; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Rizzuto G; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA., Altan-Bonnet G; Programs in Computational Biology & Immunology, Memorial Sloan Kettering, New York, NY 10065, USA., Merghoub T; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: merghout@mskcc.org., Wolchok JD; Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: wolchokj@mskcc.org. |
المصدر: | Immunity [Immunity] 2016 Jan 19; Vol. 44 (1), pp. 179-193. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
مواضيع طبية MeSH: | CD4-Positive T-Lymphocytes/*immunology , Melanoma, Experimental/*immunology , Tumor Escape/*immunology, Adoptive Transfer ; Animals ; Cell Separation ; Flow Cytometry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout |
مستخلص: | Current approaches to cancer immunotherapy aim to engage the natural T cell response against tumors. One limitation is the elimination of self-antigen-specific T cells from the immune repertoire. Using a system in which precursor frequency can be manipulated in a murine melanoma model, we demonstrated that the clonal abundance of CD4(+) T cells specific for self-tumor antigen positively correlated with antitumor efficacy. At elevated precursor frequencies, intraclonal competition impaired initial activation and overall expansion of the tumor-specific CD4(+) T cell population. However, through clonally derived help, this population acquired a polyfunctional effector phenotype and antitumor immunity was enhanced. Conversely, development of effector function was attenuated at low precursor frequencies due to irreversible T cell exhaustion. Our findings assert that the differential effects of T cell clonal abundance on phenotypic outcome should be considered during the design of adoptive T cell therapies, including use of engineered T cells. (Copyright © 2016 Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | R25 CA020449 United States CA NCI NIH HHS; R01-AI083408 United States AI NIAID NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R01-AI116863 United States AI NIAID NIH HHS; R01 CA056821 United States CA NCI NIH HHS; R01CA56821 United States CA NCI NIH HHS |
تواريخ الأحداث: | Date Created: 20160121 Date Completed: 20160607 Latest Revision: 20240325 |
رمز التحديث: | 20240325 |
مُعرف محوري في PubMed: | PMC4996670 |
DOI: | 10.1016/j.immuni.2015.12.018 |
PMID: | 26789923 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1097-4180 |
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DOI: | 10.1016/j.immuni.2015.12.018 |