{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Alizadeh D"],"funding":["NCI NIH HHS","California Institute for Regenerative Medicine","Mustang Bio. Inc.","Cancer Center Support"],"pagination":["2248-2265"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8561746"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(9)"],"pubmed_abstract":["Chimeric 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. IFNγ production by CAR T cells and IFNγ 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 IL13Rα2-CAR T cells activate patient-derived endogenous T cells and monocytes/macrophages through IFNγ 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 permissible for eliciting endogenous antitumor immunity. SIGNIFICANCE: Our findings highlight the critical role of IFNγ 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.<i>This article is highlighted in the In This Issue feature, p. 2113</i>."],"journal":["Cancer discovery"],"pubmed_title":["IFNγ Is Critical for CAR T Cell-Mediated Myeloid Activation and Induction of Endogenous Immunity."],"pmcid":["PMC8561746"],"funding_grant_id":["R01-CA236500","K00 CA234923","P30 CA033572","CA234923","R01 CA236500","P30 CA33572","F99 CA234923","CLIN2-10248","P01 CA244118"],"pubmed_authors":["Ribas A","Gholamin S","Larmonier CB","Jeppson JD","Wang D","Larmonier N","Alizadeh D","Maker M","Aftabizadeh M","Pecoraro JR","Forman SJ","Yang X","Badie B","Starr R","Brown CE","Chen MH","Wong RA","Aguilar B","Wu X"],"additional_accession":[]},"is_claimable":false,"name":"IFNγ Is Critical for CAR T Cell-Mediated Myeloid Activation and Induction of Endogenous Immunity.","description":"Chimeric 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. IFNγ production by CAR T cells and IFNγ 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 IL13Rα2-CAR T cells activate patient-derived endogenous T cells and monocytes/macrophages through IFNγ 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 permissible for eliciting endogenous antitumor immunity. SIGNIFICANCE: Our findings highlight the critical role of IFNγ 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.<i>This article is highlighted in the In This Issue feature, p. 2113</i>.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2024-11-09T11:56:08.086Z","creation":"2024-11-09T11:56:08.086Z"},"accession":"S-EPMC8561746","cross_references":{"pubmed":["33837065"],"doi":["10.1158/2159-8290.cd-20-1661","10.1158/2159-8290.CD-20-1661"]}}