Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy

摘要: Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR has largely unsuccessful to date, partly because tumor-induced immunosuppressive mechanisms, adenosine production. Previous studies shown that generated by tumor potently inhibits endogenous antitumor cell responses through activation 2A receptors (A2ARs). Herein, we observed resulted increased A2AR expression suppression both murine human cells. This was reversible either antagonists or genetic targeting shRNA. In 2 syngeneic HER2+ self-antigen models, found pharmacological the profoundly efficacy, particularly when combined with PD-1 blockade. Mechanistically, this associated cytokine production CD8+ CD4+ Given known clinical relevance CD73/adenosine pathway several types, initiation phase I trials for oncology, approach high translational potential enhance efficacy cancer types.