1. Age-associated contraction of tumor-specific T cells impairs antitumor immunity.
- Author
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Georgiev P, Han S, Huang AY, Nguyen TH, Drijvers JM, Creasey H, Pereira JA, Yao CH, Park JS, Conway TS, Fung ME, Liang D, Peluso M, Joshi S, Rowe JH, Miller BC, Freeman GJ, Sharpe AH, Haigis MC, and Ringel AE
- Abstract
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 pre-clinical models of aging and cancer.
- Published
- 2024
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