Dexamethasone Enhances CAR T Cell Persistence and Function by Upregulating Interleukin 7 Receptor
Munoz, A.; Urak, R.; Taus, E.; Hsieh, H.-J.; Jin, K.; Lin, S.-H.; Awuah, D.; Vyas, V.; Priceman, S. J.; Clark, M.; Forman, S.; Wang, X.
Show abstract
Dexamethasone (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 (IL7R) on CAR T cells and induced expression of genes involved in activation, migration, and persistence. The ex vivo upregulation of IL7R 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.
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