Abstract IA005: From hematopoiesis to immunity: Delineating the impact of aging on B-cell acute lymphoblastic leukemia progression

Abstract

Abstract The world’s aging population, those 65 and older, is projected to increase from 703 million people to 1.5 billion people by 2050. This great accomplishment comes with the added obligation of providing adequate healthcare for this vulnerable population given the number of diseases that manifest with age, including cancer. Chronic inflammation is a well-established hallmark of aging, and we have demonstrated that this state compromises hematopoiesis, notably the function of B-progenitor cells. Furthermore, we have shown that aging-associated functional declines in B-progenitor cells can be rescued with the anti-inflammatory cytokine interleukin-37, which also reduces the expression of checkpoint proteins on aged innate immune cells and augments the function of aged lymphocytes. Importantly, interleukin-37-mediated improvements in hematopoiesis and immunity suppress B-cell acute lymphoblastic leukemia (B-ALL) progression and enhance the protective capacity of aged chimeric antigen receptor (CAR) T-cells in murine models of B-ALL. Our results highlight the therapeutic potential of anti-inflammatory agents in treating hematological malignancies and suggest that combining anti-inflammatory cytokine treatment with immunotherapy strategies may represent a novel approach for treating aging-associated blood cancers. Citation Format: Curtis J. Henry. From hematopoiesis to immunity: Delineating the impact of aging on B-cell acute lymphoblastic leukemia progression [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 IA005.