Issues

To escape immune checkpoint blockade's antitumor effects, some cancers downregulate MHC-I, reducing antigen presentation. Gu, Zhang, Wang, Jiang, and colleagues found that TRAF3, a cytoplasmic signal-transduction protein and NFκB pathway inhibitor, was a negative regulator of MHC-I expression. Traf3-knockout mice exhibited enhanced T cell–mediated cytotoxicity toward tumor cells, and immune checkpoint blockade efficacy was enhanced in these mice. Traf3 knockout also resulted in a distinctive transcriptional profile that correlated with the transcriptional profiles of human melanomas that had greater MHC-I expression; patients with these profiles had better median survival. Finally, a drug screen identified birinapant as being capable of mimicking the effects of Traf3 knockout in mice. For more information, see the article by Gu, Zhang, Wang, Jiang, and colleagues on page 1524.