SMAD4, activated by the TCR-triggered MEK/ERK signaling pathway, critically regulates CD8+ T cell cytotoxic function.

The article discusses Transforming growth factor is well known to restrain cytotoxic T cell responses to maintain self-tolerance and to promote tumor immune evasion. In this study, we have investigated the role of SMAD4, a core component in the TGF signaling pathway, in CD8+ T cells. Unexpectedly, we found that SMAD4 was critical in promoting CD8+ T cell function in both tumor and infection models.