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IFN? is critical for CAR T cell-mediated myeloid activation and induction of endogenous immunity

dc.rights.licenseopenen_US
dc.contributor.authorALIZADEH, D.
dc.contributor.authorWONG, R.A.
dc.contributor.authorGHOLAMIN, S.
dc.contributor.authorMAKER, M.
dc.contributor.authorAFTABIZADEH, M.
dc.contributor.authorYANG, X.
dc.contributor.authorPECORARO, J.R.
dc.contributor.authorJEPPSON, J.D.
dc.contributor.authorWANG, D.
dc.contributor.authorAGUILAR, B.
dc.contributor.authorSTARR, R.
dc.contributor.authorLARMONIER, C.B.
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorLARMONIER, Nicolas
dc.contributor.authorCHEN, M.-H.
dc.contributor.authorWU, X.
dc.contributor.authorRIBAS, A.
dc.contributor.authorBADIE, B.
dc.contributor.authorFORMAN, S.J.
dc.contributor.authorBROWN, C.E.
dc.date.accessioned2022-05-02T08:11:32Z
dc.date.available2022-05-02T08:11:32Z
dc.date.issued2021-04-09
dc.identifier.issn2159-8274en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/139947
dc.description.abstractEnChimeric antigen receptor (CAR) T cells mediate potent antigen-specific antitumor activity; however, their indirect effects on the endogenous immune system are not well characterized. Remarkably, we demonstrate that CAR T-cell treatment of mouse syngeneic glioblastoma (GBM) activates intratumoral myeloid cells and induces endogenous T-cell memory responses coupled with feed-forward propagation of CAR T-cell responses. IFN? production by CAR T cells and IFN? responsiveness of host immune cells are critical for tumor immune landscape remodeling to promote a more activated and less suppressive tumor microenvironment. The clinical relevance of these observations is supported by studies showing that human IL13R?2-CAR T cells activate patient-derived endogenous T cells and monocytes/macrophages through IFN? signaling and induce the generation of tumor-specific T-cell responses in a responding patient with GBM. These studies establish that CAR T-cell therapy has the potential to shape the tumor microenvironment, creating a context permis-sible for eliciting endogenous antitumor immunity. Significance: Our findings highlight the critical role of IFN? signaling for a productive CAR T-cell therapy in GBM. We establish that CAR T cells can activate resident myeloid populations and promote endogenous T-cell immunity, emphasizing the importance of host innate and adaptive immunity for CAR T-cell therapy of solid tumors.
dc.language.isoENen_US
dc.title.enIFN? is critical for CAR T cell-mediated myeloid activation and induction of endogenous immunity
dc.typeArticle de revueen_US
dc.identifier.doi10.1158/2159-8290.CD-20-1661en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
dc.identifier.pubmedPMC8561746en_US
bordeaux.journalCancer Discoveryen_US
bordeaux.page2248-2265en_US
bordeaux.volume11en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.issue9en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03656363
hal.version1
hal.date.transferred2022-05-02T08:11:34Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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