Complement is mechanistically required for IDO-blockade to synergize with chemo-radiation therapy. GL261 tumors were grown in syngeneic WT (upper panel) or complement C3-deficient (lower panel) host mice. Kaplan-Meier survival plots are shown, comparing mice treated with: A, temozolomide plus radiation (TMZ + RT) and with or without IDO-blockade using DL-1MT; or B, cyclophosphamide plus radiation (CPM + RT) and with or without DL-1MT. DL-1MT (4 mg/mL) was supplied in drinking water continuously starting at day 7 after tumor implantation; chemotherapy (TMZ, 100 mg/kg; or CPM, 100 mg/kg) was given on day 9, and RT (500 cGy) was given on day 10. For reference, each survival plot contains a cohort of untreated host mice. Cohort sizes (n) are indicated for each treatment group and represent pooled data from multiple experiments containing 1–3 mice from each group per experiment. *, P < 0.0001 (vs. mice treated with chemo-radiation alone); n.s., not significant (vs. mice treated with chemo-radiation alone), by log-rank test.