Immunodynamics of explanted human tumors for immuno‐oncology

Agathe Dubuisson(Inserm), Jean‐Eudes Fahrner(Transgene (France)), Anne‐Gaëlle Goubet(Inserm), Safae Terrisse(Inserm), N. Voisin(Inserm), Charles Bayard(Inserm), Sébastien Lofek(Inserm), Damien Drubay(Inserm), Delphine Bredel(Inserm), Séverine Mouraud(Inserm), Sandrine Susini(Inserm), Alexandria P. Cogdill(The University of Texas MD Anderson Cancer Center), Lucas Rebuffet(Inserm), Elise Ballot(Inserm), Nicolas Jacquelot(The University of Melbourne), Vincent de Montpréville(Hôpital Marie Lannelongue), Odile Casiraghi(Institut Gustave Roussy), C. Radulescu(Hôpital Foch), Sophie Ferlicot(Bicêtre Hospital), David J. Figueroa(GlaxoSmithKline (United States)), Sapna Yadavilli(GlaxoSmithKline (United States)), Jeremy D. Waight(GlaxoSmithKline (United States)), Marc Ballas(GlaxoSmithKline (United States)), Axel Hoos(GlaxoSmithKline (United States)), Thomas Condamine(Incyte (United States)), Bastien Parier(Bicêtre Hospital), C. Gaudillat(Hôpital Saint Joseph), Bertrand Routy(Centre Hospitalier de l’Université de Montréal), François Ghiringhelli(Inserm), Lisa Derosa(Institut Gustave Roussy), Ingrid Breuskin(Université Paris-Saclay), Mathieu Rouanne(Université de Versailles Saint-Quentin-en-Yvelines), Fabrice André(Université Paris-Saclay), C. Lebâcle(Bicêtre Hospital), Hervé Baumert(Institut Gustave Roussy), Marie Wislez(Université Paris Cité), Élie Fadel(Hôpital Marie Lannelongue), Isabelle Cremer(Inserm), Laurence Albigès(Institut Gustave Roussy), Birgit Geoerger(Université Paris-Saclay), Jean‐Yves Scoazec(Institut Gustave Roussy), Yohann Loriot(Institut Gustave Roussy), Guido Kroemer(Karolinska University Hospital), Aurélien Marabelle(Université Paris-Saclay), Mélodie Bonvalet(Institut Gustave Roussy), Laurence Zitvogel(Inserm)
EMBO Molecular Medicine
December 29, 2020
Cited by 37Open Access
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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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