TGFβ1-Mediated SMAD3 Enhances PD-1 Expression on Antigen-Specific T Cells in Cancer.

ABSTRACT: Programmed death-1 (PD-1) is a coinhibitory receptor that downregulates the activity of tumor-infiltrating lymphocytes (TIL) in cancer and of virus-specific T cells in chronic infection. The molecular mechanisms driving high PD-1 expression on TILs have not been fully investigated. We demonstrate that TGFβ1 enhances antigen-induced PD-1 expression through SMAD3-dependent, SMAD2-independent transcriptional activation in T cells in vitro and in TILs in vivo The PD-1^hi subset seen in CD8⁺ TILs is absent in Smad3-deficient tumor-specific CD8⁺ TILs, resulting in enhanced cytokine production by TILs and in draining lymph nodes and antitumor activity. In addition to TGFβ1's previously known effects on T-cell function, our findings suggest that TGFβ1 mediates T-cel

SUBMITTER: Park BV 

PROVIDER: S-EPMC5295786 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature