Abstract B015: Racial differences in epigenetic aging and its impact on expression of T-cell inhibitory receptors

Abstract

Abstract Introduction: Accelerated aging is associated with lifetime stress and frailty, and has been reported in aging-related disease and mortality, including lung cancer, postmenopausal breast cancer, childhood cancer, and coronary heart disease. However, current knowledge on the impact of epigenetic aging in anti-tumor immunity remains limited. Pre-existing immune status heavily contributes to cancer diagnosis and the success of immunotherapy treatment, therefore, the relationship between epigenetic aging and immune function, and how it may lead to racial health disparity needs to be further explored. Methods: Genome-wide DNA methylation analysis were conducted in a feasibility test of 16 participants with equal number of African Americans (AAs) and European Americans (EAs), and epigenetic age (mAge) were calculated using R package methylclock for the established multi-tissue epigenetic clock algorithms which consists of 353 CpGs by Horvath. Correlation analysis was performed between mAge and in vitro T cell activation tests. Results: As expected, high correlation of calculated mAge versus chronological age was observed from 16 participants using the Horvath calculator, with higher mAge in AAs than EAs. Significant separation in DNA methylation profiles between AAs and EAs existed based on the top 1,000 CpG sites from the principal component analysis. To understand the effects of aging on T cell function, a series of functional assays were performed from different age groups, and significant (P<0.05) negative correlations of Age and mAge to flow cytometry defined naïve lymphocyte subsets were detected. Significant positive correlations between mAge and the expression of T-cell inhibitory receptors CTLA4 and TIGIT were observed in activated T cells from this sample population. Conclusion: The human immune system undergoes dramatic aging-related changes, which continuously progress and contribute to the decline in immune-mediated protection against infections and cancer. Our study serves as a proof-of-principle to highlight the degree of accelerated epigenetic aging and its impact on T cells function among different racial and age groups), which warrants further research that may shed more light into therapeutic cellular immune responses and mechanisms of immune-related adverse events in patients treated with immunotherapy for cancer. Citation Format: Ping-Ching Hsu, Michael Bauer, Tung-Chin Chiang, Lora J. Rogers, A. Murat Aydin, L. Joseph Su, Brian Koss. Racial differences in epigenetic aging and its impact on expression of T-cell inhibitory receptors [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B015.