GSDMD is required for effector CD8+ T cell responses to lung cancer cells.

GSDMD is a recently discovered pyroptosis executioner in monocytes whose N-terminal domain can insert into the inner leaflet of cell membranes and form extensive pores. However, the function of GSDMD in other biological systems remains unclear. In this study, we showed that the expression of GSDMD was consistently correlated with CD8+ T cell markers in The Cancer Genome Atlas (TCGA) cohorts. GSDMD cleavage increased in OT-1 cytotoxic T lymphocytes (CTLs) and human activated CD8+ T cells. Colocalization of GSDMD with granzyme B was observed in the proximity of immune synapses, and GSDMD deficiency reduced the cytolytic capacity of CD8+ T cells. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in CTLs and demonstrated that GSDMD is required for an optimal CTL response to cancer cells.