The anti-tumor response to ASTX660+XRT is predominantly driven by CD8 + T cells and, to a lesser degree, NK cells. (A) 5 × 106 MOC1 cells were implanted into the right hind leg of wildtype female C57BL/6 mice. Mice were randomized into 5 groups (vehicle control, daily ASTX660 with 2 doses of XRT, ASTX660+XRT with anti-TNFα twice weekly, ASTX660+XRT with anti-CD8 twice weekly, or ASTX660+XRT with anti-NK1.1 twice weekly) of 10 mice each starting 12 days after tumor inoculation. ASTX660 treatment began on day 12 with daily treatments via oral gavage for two full weeks with one week off in between (orange arrows). XRT was given in two doses of 8 Gy each on days 2 and 4 of treatment (brown arrows). Blocking antibodies were given twice weekly (blue arrows). A more detailed treatment schema is available in Supplementary Figure S3C. Error bars represent standard error of the mean. *p < 0.05, **p < 0.01 versus control, #p < 0.05, ##p < 0.01 versus ASTX660+XRT, ++p < 0.01 vs. ASTX660+XRT+Anti-CD8. (B) Kaplan-Meier survival curves representing each treatment group.