Rebalancing TGFβ1/BMP signals in exhausted T cells unlocks responsiveness to immune checkpoint blockade therapy.

T cell dysfunctionality prevents the clearance of chronic infections and cancer. Furthermore, epigenetic programming in dysfunctional CD8 T cells limits their response to immunotherapies, including immune checkpoint blockade (ICB). However, it is unclear which upstream signals drive acquisition of dysfunctional epigenetic programs, and whether therapeutically targeting these signals can remodel terminally dysfunctional T cells to an ICB-responsive state.