Method to treat and stratificate a patient sufferingfrom a cancer

The present invention relates to the stratification and treatment of patients suffering of cancer. Due to the fact that anti-PD1 therapy targets lymphocytes and the efficiency of anti-cancer therapy is measured by the impact on the tumor cells, the inventors postulated that studying the molecular mechanisms of resistance of anti-PD1 therapy should take into consideration existing intercellular communication between lymphocytes and tumor cells. As exosomes are the carriers for the intercellular transfer of the miRNA responsible of chemoresistance, they herein investigated whether exposure of T cells to anti-PD1 therapy might promote the expression of exosomal miRNA (exomiR) causing the chemoresistance of cancer cells. Surprisingly, they found that anti-PD1 exposure of T-cell promotes an enrichment of exosomal miRNA-4315. They also noted that exosomal miRNA-4315 induced a phenomenon of apopto-resistance to conventional chemotherapies in cancer cells receiving exosomal miRNA-4315. At molecular level, they discern that the apopto-resistance phenomenon was associated with the miRNA-4315-mediated down-regulation of Bim, a pro-apoptotic protein. In cellular and mice models, they observed that the BH3 mimetic agent ABT263 circumvented this resistance. Thus, the invention relates to methods of stratification using exosomal miRNA-4315 and method of treatment of patients suffering of cancer using BH3 mimetic agent.

Keywords: Exoxome, PD1 treatment response prediction, Pan-Cancer
Patent Application number: EP20306025.6 on 14/09/2020
PCT/EP2021/075132 on 13/09/2021
Cell Death Dis. 2020 Dec 11;11(12):1048. Guyon et al. Anti-PD1 therapy induces lymphocyte-derived exosomal miRNA-4315 release inhibiting Bim-mediated apoptosis of tumor cells doi: 10.1038/s41419-020-03224-z.

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