Thursday Seminar: Team Sisirak



Dr Jean Pierre Pouget et Dr. Julie Constanzo


Role of extracellular vesicles in and DNA sensing in the activation anti-tumor immune responses induced by targeted radiotherapy. Resume: Dr. Jean-Pierre Pouget is an INSERM director of research with a renowned expertise in the development of novel radiotherapeutic approaches to treat cancer. He directs the laboratory of “Radiobiology for Targeted and Personalized Radiotherapy” at the IRCM in Montpellier. Together with Dr. Julie Constanzo they developed and optimized a novel radiotherapy approach for cancer called targeted radionuclide therapy (TRT). TRT consists of a delivery of low-dose radiation over long periods of time by the administration of a radiolabeled antibodies targeting specific molecules expressed on tumors (antigens). This approach allows a specific irradiation of tumor cells that overexpress the targeted antigen, while minimizing exposure of healthy tissues. Interestingly, they show that this approach efficiently eliminates established tumors, but to do so it requires a fully functional immune system. Indeed, such TRT approach boosts the establishment of antitumor immune responses and protects immunocompetent hosts from secondary tumor challenge. Mechanistically, TRT contribute to the secretion of exosomes by tumors which are responsible for the activation of anti-tumor immune responses. Accordingly, vaccination with exosomes originating from TRT treated tumor cells delays tumor growth in vivo while the inhibition of exosome formation in vivo reduced the therapeutic potential of TRT. The activation of the immune system by TRT is likely due to the DNA present within exosomes inducing the production of type I interferons upon its sensing by innate immune DNA sensor cyclic GMP-AMP synthase (cGAS). Therefore, the team of Jean-Pierre Pouget has developed a novel radiotherapy approach targeting both tumor cells and stimulating anti-tumor immune responses that hold great promise in the treatment of cancer patients.

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