Fig. 1

IFN-γ enhances CAR-T anti-tumor activities by sensitizing tumor cells expressing ICAM-1. a, b IFN-γ priming to tumor cells enhances the specific cytolytic ability and IFN-γ secretion of HER2-CAR (a) and MSLN-CAR T (b). c The blockage to IFN-γ by using neutralizing antibody decreases the lytic ability of HER2-CAR T cells. d, e Tumor cells were primed by IFN-γ for 24 h, then were washed using fresh culture media to remove IFN-γ. Sufficient anti-IFN-γ neutralizing antibody was used to block IFN-γ release by CAR-T cells (d). The specific lysis was measured by LDH assay (e). f IFN-γR2 knockout in tumor cells significantly decreased CAR-T cytotoxicity. g IFN-γR2 knockout impaired the enhancement of IFN-γ-priming to CAR-T cytotoxicities. h PD-L1-overexpression did not decrease CAR-T cytotoxicity to tumor cells. i IFN-γ-priming enhanced CAR-T-specific lysis to tumor cells overexpressing PD-L1. j, k PD-L1-overexpression in IFN-γR2-deficient tumor cells inhibited CAR-T cytotoxicity (j) and cytokines release (k). l The knockout of ICAM-1 in tumor cells impaired the enhancement of IFN-γ-priming to CAR-T cytotoxicity. m The overexpression of ICAM-1 in IFN-γR2 KO tumor cells enhanced CAR-T cytotoxicity and the secretion of IFN-γ and IL-2. n The enhancement of IFN-γ priming to the serial cytotoxic ability of CAR-T cells. o The relatively increased RNA expression of Bcl-2, Bcl-xl, survivin in CAR-T cells that encountered IFN-γ-primed tumor cells. p The procedure of combinational therapy of IFN-γ and HER2-CAR T cells in peritoneal ovarian cancer models in B-NSG mice. IFN-γ was administrated (25 μg per mouse) prior to CAR-T cells. IP, intraperitoneal injection. q Bioluminescent images and quantitative analysis of peritoneal metastases of human ovarian cancer in selected timepoints during the experiments. Bars represent the mean ± s.e.m. p-values determined by unpaired two-tailed t-tests. *p < 0.05, **p < 0.01, ***p < 0.001