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 (7, 11, 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)

1 UMR 1015 - Immunologie des tumeurs et immunothérapie
2 SBE - Service de biostatistique et d'épidémiologie
3 CESP - Centre de recherche en épidémiologie et santé des populations
4 The University of Texas M.D. Anderson Cancer Center [Houston]
5 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
6 WEHI - The Walter and Eliza Hall Institute of Medical Research
7 Département de biologie et pathologie médicales [Gustave Roussy]
8 Centre hospitalier Saint-Joseph [Paris]
9 CR CHUM - Centre de Recherche du Centre Hospitalier de l’Université de Montréal
10 Département de médecine oncologique [Gustave Roussy]
11 Hôpital Foch [Suresnes]
12 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
13 Direction de la recherche [Gustave Roussy]
14 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
15 CHU Tenon [AP-HP]
16 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
17 UMR 8203 - Vectorologie et thérapeutiques anti-cancéreuses [Villejuif]
18 AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
19 HEGP - Hôpital Européen Georges Pompidou [APHP]
20 Karolinska University Hospital [Stockholm]

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.

Keywords: cancer; immune checkpoint inhibitors; immunomonitoring; precision oncology; “in sitro” assay

Domains: Life Sciences [q-bio]

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, 2021, 13 (1), ⟨10.15252/emmm.202012850⟩. ⟨hal-03127487⟩