Fig. 6.

Promoting the type 1 immune response of O-HSV1211 enhanced antitumor function. A–C Coculture of tumor cells with CD4⁺ or CD8⁺ T cells. Tumor cells were cultured in plates precoated with anti-CD3 and anti-CD28 antibodies for 48 h and infected with O-HSV1 and O-HSV1211 at an MOI of 1. CD4⁺ or CD8⁺ T cells were isolated and activated for 24 h and cocultured with infected SW620 or MC38 cells. A IFN-γ production in CD4⁺ and CD8⁺ T cells was analyzed by flow cytometry with a fluorescence-conjugated antibody. B Tumor cells were counted under a microscope (n=3). C Anti-IFN-γ (XMG1.2) antibody was used in the CD8⁺ and CD4⁺ T-cell coculture system to neutralize IFN-γ, and tumor cells were counted under a microscope (n=3). D Experimental schema. Sex and age matched C57BL/6J mice were implanted with MC38 tumor cells (1×10⁵cells) on Day 0, and treated intratumorally with oncolytic viruses or PBS on Days 7, 10 and 13 (black arrows). Anti-IFN-γ antibody (5 mg/kg) or isotype control IgG (5 mg/kg rat IgG) was injected intraperitoneally on Days 7, 10, 13 and 16 post tumor implantations (red arrows). E The survival of tumor-bearing mice treated with O-HSV1 or O-HSV1211 plus isotype or anti-IFN-γ antibody was plotted using the Kaplan–Meier method. F Tumor growth in experiment E was measured every 3rd day (n=6). Tumor volumes are presented as the mean values ± standard deviation and analyzed by Student's t test. ns, not significant, *p < 0.05, **p < 0.01, ***p < 0.001.