studying-chronic-exposure-of-mice-to-ultraviolet-b-radiation

Studying Chronic Exposure of Mice to Ultraviolet B Radiation 

Ultraviolet B (UVB) radiation (280-320 nm) has been recognized as a carcinogen since 1928, leading to sun exposure minimization. However, epidemiological ...

The Ragon Institute of Mass General, MIT, and Harvard Main Street

The Hungry Side of Skin.

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 T-cell subpopulation. Independently of the UV effect, Ly6a T cells are induced by chronic type-1 interferon in the tumor microenvironment. Treatment with an anti-Ly6a antibody enhances the anti-tumoral cytotoxic activity of T cells and reprograms their mitochondrial metabolism via the Erk/cMyc axis. Treatment with an anti-Ly6a antibody inhibits tumor growth in mice resistant to anti-PD1 therapy. Applying our findings in humans could lead to an immunotherapy treatment for patients with resistance to existing treatments.

Article	Year
The Hungry Side of Skin. The Journal of investigative dermatology\| PubMed ID: 39217538	2024
Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy. Nature communications\| PubMed ID: 39333093	2024

Shivang Parikh

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