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Immunodynamics of explanted human tumors for immuno-oncology

Agathe Dubuisson 1 Jean Eudes Fahrner 1 Anne Gaëlle Goubet 1 Safae A. Terrisse 1 Nicolas Voisin 1 Charles Bayard 1 Sébastien Lofek 1 Damien Drubay 2, 3 Delphine Bredel 1 Séverine Mouraud 1 Sandrine Susini 1 Alexandria P. Cogdill 1, 4 Lucas Rebuffet 1 Elise Ballot 5 Nicolas Jacquelot 6 Vincent Thomas de Montpreville Odile Casiraghi 7 Camélia Radulescu Sophie Ferlicot David J. Figueroa Sapna Yadavilli Jeremy D. Waight Marc S. Ballas Axel X. Hoos Thomas Condamine Bastien Parier Christophe Gaudillat 8 Bertrand Routy 9 François Ghiringhelli 5 Lisa Derosa 10 Ingrid Breuskin Mathieu Rouanne 11, 7, 12 Fabrice André 13 Cédric Lebacle Hervé Baumert Marie Wislez 14, 15 Élie Fadel Isabelle Cremer 16 Laurence Albiges 1, 10 Birgit Geoerger 17, 13 Jean Yves Scoazec 1, 18 Yohann Loriot 1, 10 Guido Kroemer 16, 19, 20 Aurélien Marabelle 18 Mélodie Bonvalet 18 Laurence Zitvogel 1, * 
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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Submitted on : Thursday, June 2, 2022 - 4:38:05 PM
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Agathe Dubuisson, Jean Eudes Fahrner, Anne Gaëlle Goubet, Safae A. Terrisse, Nicolas Voisin, et al.. Immunodynamics of explanted human tumors for immuno-oncology. EMBO Molecular Medicine, Wiley Open Access, 2021, 13 (1), ⟨10.15252/emmm.202012850⟩. ⟨hal-03127487⟩

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