Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity.

Autor:	Georgiev P; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Han S; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Huang AY; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.; Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts., Nguyen TH; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Drijvers JM; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Creasey H; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Pereira JA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Yao CH; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Park JS; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Conway TS; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Fung ME; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Liang D; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Peluso M; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Joshi S; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Rowe JH; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Miller BC; Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Freeman GJ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Sharpe AH; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Haigis MC; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Ringel AE; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, Massachusetts.; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2024 Nov 04; Vol. 12 (11), pp. 1525-1541.
DOI:	10.1158/2326-6066.CIR-24-0463
Abstrakt:	Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as preclinical models of aging and cancer. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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