Radiotherapy-Induced Overexpression of Exosomal Mirna-378A-3P in Cancer Cells Limits Natural Killer Cells Cytotoxicity

Abstract

<b>Aim:</b> 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. <b>Materials & methods:</b> Our study included the use of different cancer cell lines, blood biopsies of xenograph mice model and patients treated with radiotherapy. <b>Results:</b> 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. <b>Conclusion:</b> 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.