Dexamethasone Enhances CAR T Cell Persistence and Function by Upregulating Interleukin 7 Receptor

Abstract

AbstractDexamethasone (dex) is a glucocorticoid that is a mainstay for treatment of inflammatory pathologies, including immunotherapy-associated toxicities. Dex suppresses the endogenous immune response and is also believed to suppress the function of chimeric antigen receptor (CAR) T cells. However, recent reports observed higher CAR T cell numbers in patients treated with dex, highlighting the rationale for interrogating the specific effects of dex on CAR T cells. Here, we found that dex did not inhibit CAR T cell expansion or function. A single dose of dex during the manufacturing process upregulated the pro-persistence interleukin 7 receptor α (IL7Rα) on CAR T cells and induced expression of genes involved in activation, migration, and persistence. The ex vivo upregulation of IL7Rα induced by dex significantly enhanced CAR T cell persistence and anti-tumor efficacy in vivo when combined with exogenous IL-7. Moreover, the combination of dex and IL-7 resulted in increased persistence of CAR T cells and led to complete remission of mice. Overall, our studies in both in vitro and in vivo treatment support a positive role of dex on CAR T cell potency and provide insight into the application of glucocorticoids in cellular anti-cancer therapy.