Immunodynamics of explanted human tumors for immuno-oncology.
Agathe DubuissonJean-Eudes FahrnerAnne-Gaëlle GoubetSafae TerrisseNicolas VoisinCharles BayardSebastien LofekDamien DrubayDelphine BredelSéverine MouraudSandrine SusiniAlexandria CogdillLucas RebuffetElise BallotNicolas JacquelotVincent Thomas De MontprevilleOdile CasiraghiCamélia RadulescuSophie FerlicotDavid J FigueroaSapna YadavilliJeremy D WaightMarc BallasAxel HoosThomas CondamineBastien ParierChristophe GaudillatBertrand RoutyFrançois GhiringhelliLisa DerosaIngrid BreuskinMathieu RouanneFabrice AndréCédric LebacleHervé BaumertMarie WislezElie FadelIsabelle CremerLaurence AlbigesDidier FrappazJean-Yves ScoazecYohann LoriotGuido KroemerAurélien MarabelleMélodie BonvaletLaurence ZitvogelPublished in: EMBO molecular medicine (2020)
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.