Fig. 9.

GPR84 antagonism combined with anti-PD-1 therapy enhances antitumor immunity. a Gross and microscopic specimens of esophageal tumors produced in response to 4-NQO stimulation in WT and GPR84^−/− mice administered anti-PD-1 or IgG. b Overall survival of 4-NQO-challenged WT and GPR84^−/− mice administered anti-PD-1 or IgG, analyzed by the Kaplan–Meier method. c Percentages of CD3⁺CD8⁺ T cells and CD8⁺CD69⁺ T cells in the peripheral blood and spleen of 4-NQO-challenged WT and GPR84^−/− mice treated with anti-PD-1 or IgG were analyzed by flow cytometry. d Immunofluorescence analysis of CD8 (green) expression in esophageal cancer tissues from 4-NQO-challenged WT and GPR84^−/− mice treated with anti-PD-1 or IgG; DAPI (blue), CD8 (green). e Tumor volumes in WT and GPR84^−/− mice administered anti-PD-1 or IgG measured from days 10 to 26 after LLC-cell injection. Relative expression of ARG1, CYBB, iNOS, IL-10, NCF4, and TGF-β2 in purified MDSCs (f) and percentages of IFN-γ, granzyme B, and perforin in CD3⁺CD8⁺ T cells from spleen (g) and tumor tissues (h) of LLC-cell-injected WT and GPR84^−/− mice administered anti-PD-1 or IgG analyzed by qPCR and flow cytometry, respectively. i Heat map depicting the expression of T cell activation and function-related molecules in WT and GPR84^−/− mice administered anti-PD-1 or IgG treatment. j Tumor volumes measured on days 10 and 25 after LLC-cell-luciferase implantation before and after treatment with anti-PD-1 and GPR84 antagonist using an in vivo imaging system. k Statistical graph depicting the tumor volumes as a function of fluorescence intensity. l Measurement of the xenografts from days 10 to 25 after cell implantation before and after administration of anti-PD-1 and GPR84 antagonist. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001