TGFβ1 and BMP signals modulate CD8+ T cell functionality and responsiveness to immune checkpoint blockade therapy

Abstract T cell dysfunctionality is a major challenge during chronic infections and cancer, limiting durable responses to T-cell based immunotherapies including immune checkpoint blockade (ICB). However, the role of upstream environmental signals in modulating development terminal dysfunction CD8+ cells remains be explored. We have recently established that persistent TGFβ1 exposure drives an epigenetically stabilized, program chronically stimulated human mouse cells. In contrast, boosting BMP signaling induces striking ability maintain effector functionality survival under stimulation. Here, we show how rebalancing TGFβ1/BMP-signals dysfunctional retains cord blood or tumor-infiltrating vitro, while enhancing virus tumor control mice. also explore therapeutic potential BMP-signals promoting durability responses. Altogether, these findings provide exciting new approach enhance immunotherapy.