Abstract 3921: The aged tumor microenvironment limits CD8+ T cell control of cancer

Abstract Aging is associated with progressive loss of immune function, which parallels the rise in cancer incidence. The etiology and impact of age-related CD8+ T cell dysfunction in cancer remain poorly understood. Here, we demonstrate that increased tumor growth in aged hosts is associated with reduced CD8+ T cell infiltration and function. The transfer of young antigen-specific CD8+ T cells fails to restore tumor control in aged hosts due to the rapid induction of CD8+ T cell dysfunction. The aged tumor microenvironment drives a novel age-associated dysfunctional state (TADys) that is functionally, transcriptionally, and epigenetically distinct from canonical CD8+ T cell exhaustion. Overall, this study focuses on understanding the cell-intrinsic and -extrinsic effects on CD8+ T cell immunity in aging and explores a proper strategy to improve CD8+ T cell control of cancer. Citation Format: Alex C. Y. Chen, Sneha Jaiswal, Daniela Martinez, Cansu Yerinde, Keely Ji, Velita Miranda, Megan E. Fung, Sarah A. Weiss, Maria Zschummel, Kazuhiro Taguchi, Christopher S. Garris, Thorsten R. Mempel, Debattama R. Sen. The aged tumor microenvironment limits CD8+ T cell control of cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3921.