Fig. 8: In vivo PGRN blockade promotes antigen-specific T-cell cytotoxicity against tumors in orthotopic FKPC2GP model. | Nature Communications

Fig. 8: In vivo PGRN blockade promotes antigen-specific T-cell cytotoxicity against tumors in orthotopic FKPC2GP model.

From: Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression

Fig. 8: In vivo PGRN blockade promotes antigen-specific T-cell cytotoxicity against tumors in orthotopic FKPC2GP model.

a Timeline for treatment of anti-PGRN antibody (PAb) or mIg (50 mg/kg) in an orthotopic model of GP82 cells in C57BL/6 J mice. b Tumors and spleens of mIg-treated (n = 4) and PGRN Ab-treated (n = 4) mice with orthotopic GP82 transplantation and intravenous injection of LCMV-gp33-reactive T cells freshly isolated from P14-TCR-Tg mice. c Tumor growth was assessed by ultrasound imaging and presented as a fold change in tumor volume before and after PGRN Ab (PAb) or mIg treatment started. d Tumors were digested into disaggregated cells and stained for T-cell infiltration. Flow cytometric analysis showing the percentage of tumor-infiltrating T (CD3+) cells and the exogenously injected LCMV-gp33-reactive (CD45.1+) T cells, in tumors treated with PGRN Ab (n = 4) or mIg (n = 4). Two-tailed Mann–Whitney test. e Flow cytometric analysis showing the expression of cytotoxic markers granzyme B (GzmB), TNF, and IFNg on CD3+ T cells in tumors with PGRN Ab (n = 4) or mIg (n = 4). Two-tailed Mann–Whitney test. f IHC staining of PGRN, MHCI marker H-2Db, CD8, GzmB, and cleaved caspase 3 (Cl Casp3) in orthotopic GP82 tumors with PGRN Ab (n = 4) or mIg (n = 4). The lower panels how the percentages of positive cells in the whole tumors quantified by Definiens. Two-tailed Mann–Whitney test. Mean ± SD is shown. Scale bar unit: μm.

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