Immunodynamics of explanted human tumors for immuno-oncology

移植人肿瘤的免疫动力学及其在肿瘤免疫学中的应用

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作者:Agathe Dubuisson ,Jean-Eudes Fahrner ,Anne-Gaëlle Goubet ,Safae Terrisse ,Nicolas Voisin ,Charles Bayard ,Sebastien Lofek ,Damien Drubay ,Delphine Bredel ,Séverine Mouraud ,Sandrine Susini ,Alexandria Cogdill ,Lucas Rebuffet ,Elise Ballot ,Nicolas Jacquelot ,Vincent Thomas de Montpreville ,Odile Casiraghi ,Camélia Radulescu ,Sophie Ferlicot ,David J Figueroa ,Sapna Yadavilli ,Jeremy D Waight ,Marc Ballas ,Axel Hoos ,Thomas Condamine ,Bastien Parier ,Christophe Gaudillat ,Bertrand Routy ,François Ghiringhelli ,Lisa Derosa ,Ingrid Breuskin ,Mathieu Rouanne ,Fabrice André ,Cédric Lebacle ,Hervé Baumert ,Marie Wislez ,Elie Fadel ,Isabelle Cremer ,Laurence Albiges ,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.

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