Pyroptosis modulates multiple immune cell populations in targeted therapy-treated melanoma.

ABSTRACT: Treatment of melanoma with BRAF inhibitors plus MEK inhibitors (BRAFi + MEKi) stimulates an intratumoral immune response, in part through pyroptosis mediated by the pore-forming protein gasdermin E (GSDME/Gsdme). How GSDME mediates effects on tumoral immunity is not well characterized. Using single-cell RNA-sequencing (scRNA-seq) and flow cytometry in BRAFi + MEKi treated melanoma, we show herein that isogenic Gsdme knockout (KO) tumors show decreased infiltration with T cells, natural killer (NK) cells and regulatory T cells (Tregs) compared to control tumors. Infiltrated Tregs in Gsdme KO tumors displayed decreased expression of the interleukin 2 receptor and phenotypic markers associated with suppressive function. Furthermore, intratumoral, the frequency of phenotypically suppressive Tr

SUBMITTER: Wilski-Cronin NA 

PROVIDER: S-EPMC12851756 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature