Abstract 621: Aging dampens lymphoma-provoked phenotypic and epigenomic changes to the adaptive immune system

Abstract

Abstract Lymphoma is a disease that principally afflicts older individuals and also impairs the immune system, yet how aging and cancer interact to affect the immune system remains poorly understood. This is particularly the case for malignancies that arise within hematopoietic tissues that closely interact with immune cells. We hypothesized that lymphoma-provoked changes to the adaptive immune system would differ based on age. To explore how the immune system is altered by both B-cell lymphoma and the aging process, we transplanted Eμ-Myc lymphoma B-cells into mice aged 6-12 weeks or 20-24 months. Interestingly, as marked by reduced splenomegaly and lymphoma cell numbers, tumor burden was significantly reduced in aged hosts, suggesting lymphoma cells grow more slowly in the aged tissue microenvironment. Further, while lymphoma progression provoked losses in total numbers of normal T-cells, NK-cells, and B-cells in young individuals, aged lymphocytes were surprisingly resistant to lymphoma. Similarly, profound phenotypic changes in T-cell subpopulations that are provoked by Eμ-Myc lymphoma in young individuals, such as increases in expression of CD44, CD69, PD-1, Foxp3, and Tox, were not manifest in lymphoma-bearing aged mice. In addition, immature NK cell population dynamics were altered by lymphomas differently among aged mice when compared to young mice. Finally, analyses of the chromatin state of enriched CD4+ T cells from young and aged mice by ATAC-seq revealed that the aging process provoked marked alterations in the epigenome, and that lymphoma only provoked significant changes to the epigenome among young CD4+ T cells. We conclude that aging-driven epigenetic alterations manifest in the adaptive immune system renders these cells surprisingly resilient to lymphoma-mediated immune suppression. Citation Format: Rebecca S. Hesterberg, Chia-Ho Cheng, Jiqiang Yao, Xiaofei Song, Xiaoqing Yu, John L. Cleveland. Aging dampens lymphoma-provoked phenotypic and epigenomic changes to the adaptive immune system [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 621.