YTHDF2 inhibition promotes DC vaccine efficacy with RT. (A) B16F10-OVA tumor growth curves with indicated treatments. WT and Ythdf2-cKO DC vaccines were administered intratumorally once per week. Tumors were treated with or without IR (20 Gy) on day 9 (n = 5, mean ± SD). (B) B16F10-OVA tumor growth curves with indicated treatments. WT DCs or WT DCs treated with YTHDF2 inhibitor were administered intratumorally once per week. Tumors were treated with or without IR (20 Gy) on day 9 (n = 5, mean ± SD). (C) LLC tumor growth curves with indicated treatments. WT DCs or Ythdf2-cKO DCs were administered intratumorally once per week. Tumors were treated with or without IR (20 Gy) on day 9 (n = 5, mean ± SD). (D) Representative LLC spontaneous lung metastasis of mice receiving treatments as indicated in C; scale bars: 2 mm. (E) IFN-γ+ CD8+ T cells in lung tissue. The lung was collected on day 10 after IR treatment (n = 4, mean ± SEM). (F) ELISPOT assay of human DC to assess antigen cross-presentation capability to matched human T cells. DCs were treated with the YTHDF2 inhibitor and further cocultured with irradiated or nonirradiated HCT116 cells (n = 5, mean ± SEM). Statistical analysis was performed using two-sided unpaired Student’s t test (A–C, E, and F); *P < 0.05; **P < 0.01; ***P < 0.001.
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