Radiotherapy-Induced Overexpression of Exosomal Mirna-378A-3P in Cancer Cells Limits Natural Killer Cells Cytotoxicity
Joséphine Briand, Delphine Garnier, Arulraj Nadaradjane, K. Clément-Colmou, Vincent Potiron, S. Supiot, Gwenola Bougras-Cartron, Jean‐Sébastien Frenel, Dominique Heymann, François M. Vallette, Pierre‐François Cartron
Abstract
Aim: We here hypothesized that tumor-derived exosomal miRNA (TexomiR) released from irradiated tumors may play a role in the tumor cells escape to natural killer (NK) cells. Materials & methods: Our study included the use of different cancer cell lines, blood biopsies of xenograph mice model and patients treated with radiotherapy. Results: The irradiation of cancer cells promotes the TET2-mediated demethylation of miR-378 promoter, miR-378a-3p overexpression and its loading in exosomes, inducing the decrease of granzyme-B (GZMB) secretion by NK cells. An inverse correlation between TexomiR-378a-3p and GZMB was observed in murine and human blood samples. Conclusion: Our work identifies TexomiR-378a-3p as a molecular signature associated with the loss of NK cells cytotoxicity via the decrease of GZMB expression upon radiotherapy.