Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation.

ABSTRACT: While immunotherapy has revolutionized cancer treatment, its safety has been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory (T_reg) cell function specifically in the tumor microenvironment. T_reg cell-specific MED1 deletion does not predispose mice to autoimmunity or excessive inflammation. In contrast, MED1 is required for T_reg cell promotion of tumor growth because MED1 is required for the terminal differentiation of effector T_reg cells in the tumor. Suppression of these terminally differentiated T_reg cells is sufficient for eliciting antitumor immunity. Both human and murine T_reg cells experience divergent paths of differentiation i

SUBMITTER: Chaudhuri SM 

PROVIDER: S-EPMC10983042 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature