Abstract 5149: Age-associated remodeling of anti-tumor T cell immunity and metabolism

Abstract Aging results in remodeling of T cell immunity and is associated with poor clinical outcome in age-related diseases such as cancer. Amongst the hallmarks of aging, changes in host and cellular metabolism are critically involved in the development, maintenance, and functional responses of T cells. Although metabolic perturbations impact anti-tumor T cell responses, the link between age-associated metabolic dysfunction and anti-tumor immunity remains unclear. First, we utilized B16, MC38 and E0771 tumor-bearing young (2-4 months) and aged (18-24 months) C57BL/6 mice to examine the effects of aging on tumor growth. Aged mice exhibited accelerated tumor growth in B16, MC38 and E0771 tumor models. Flow cytometric analyses of tumor infiltrating lymphocytes (TILs) revealed distinct changes in CD8+ T cell population, decreased activation status and tumor-specificity in aged mice. Consistent with these findings, CD8+ T cells functionally played a limited role in controlling tumor growth in aged mice. Here, we will explore the mechanisms of age-associated metabolic dysfunction in T cells and its implications in anti-tumor immunity. As the average life expectancy continues to increase, understanding the interplay between age-related metabolic reprogramming and maladaptive T cell immunity will be instrumental in the development of novel therapeutic strategies for older patients. Citation Format: SeongJun Han, Peter Georgiev, Alison Ringel, Arlene Sharpe, Marcia Haigis. Age-associated remodeling of anti-tumor T cell immunity and metabolism. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5149.