Immunodynamics of explanted human tumors for immuno‐oncology
Agathe Dubuisson, Jean‐Eudes Fahrner, Anne‐Gaëlle Goubet, Safae Terrisse, N. Voisin, Charles Bayard, Sébastien Lofek, Damien Drubay, Delphine Bredel, Séverine Mouraud, Sandrine Susini, Alexandria P. Cogdill, Lucas Rebuffet, Elise Ballot, Nicolas Jacquelot, Vincent de Montpréville, Odile Casiraghi, C. Radulescu, Sophie Ferlicot, David J. Figueroa, Sapna Yadavilli, Jeremy D. Waight, Marc Ballas, Axel Hoos, Thomas Condamine, Bastien Parier, C. Gaudillat, Bertrand Routy, François Ghiringhelli, Lisa Derosa, Ingrid Breuskin, Mathieu Rouanne, Fabrice André, C. Lebâcle, Hervé Baumert, Marie Wislez, Élie Fadel, Isabelle Cremer, Laurence Albigès, Birgit Geoerger, Jean‐Yves Scoazec, Yohann Loriot, Guido Kroemer, Aurélien Marabelle, Mélodie Bonvalet, Laurence Zitvogel
Abstract
Decision making in immuno-oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno-assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti-PD-1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay.