Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy.

ABSTRACT: T cell inhibitory mechanisms prevent autoimmune reactions, while cancer immunotherapy aims to remove these inhibitory signals. Chronic ultraviolet (UV) exposure attenuates autoimmunity through promotion of poorly understood immune-suppressive mechanisms. Here we show that mice with subcutaneous melanoma are not responsive to anti-PD1 immunotherapy following chronic UV irradiation, given prior to tumor injection, due to the suppression of T cell killing ability in skin-draining lymph nodes. Using mass cytometry and single-cell RNA-sequencing analyzes, we discover that skin-specific, UV-induced suppression of T-cells killing activity is mediated by upregulation of a Ly6a^high T-cell subpopulation. Independently of the UV effect, Ly6a^high T cells are induced by chronic ty

SUBMITTER: Maliah A 

PROVIDER: S-EPMC11437002 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature