A CD4+ T lymphocyte-specific TCR/GSDMD/IL-2 axis facilitates antitumor immunity.

ABSTRACT: Gasdermin (GSDM) family proteins mediate tumor pyroptosis and impact cancer progression, but other than that, their involvement in the tumor immune microenvironment remains largely unknown. Here, we show that activation of GSDMD in human tumor specimens mainly occurs in tumor-infiltrating leukocytes. Significantly, GSDMD deficiency or its inactivation in CD4+ T cells disabled CD8+ T cell-mediated antitumor immunity and caused tumor outgrowth in mice. Further study uncovered that, via inducing IL-2 production, GSDMD was required for CD4+ T cells to provide help to CD8+ T cell function. Mechanistically, GSDMD was cleaved by TCR stimulation-activated caspase-8 to form GSDMD-N pores, which enhanced Ca2+ influx for IL-2 induction. Moreover, GSDMD activation and function were conserved in human

SUBMITTER: Yao Y 

PROVIDER: S-EPMC12321394 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature