| Autor: |
Avishai Maliah, Nadine Santana-Magal, Shivang Parikh, Sagi Gordon, Keren Reshef, Yuval Sade, Aseel Khateeb, Alon Richter, Amit Gutwillig, Roma Parikh, Tamar Golan, Matan Krissi, Manho Na, Gal Binshtok, Paulee Manich, Nadav Elkoshi, Sharon Grisaru-Tal, Valentina Zemser-Werner, Ronen Brenner, Hananya Vaknine, Eran Nizri, Lilach Moyal, Iris Amitay-Laish, Luiza Rosemberg, Ariel Munitz, Noga Kronfeld-Schor, Eric Shifrut, Oren Kobiler, Asaf Madi, Tamar Geiger, Yaron Carmi, Carmit Levy |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-52079-x |
| Popis: |
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 Ly6ahigh T-cell subpopulation. Independently of the UV effect, Ly6ahigh 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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