1. Fig. 8 Combining M7824 with radiation or chemotherapy enhances antitumor efficacy.
Combining M7824 with radiation or chemotherapy enhances antitumor efficacy. (A to C) μMt−mice were inoculated intramuscularly (i.m.) with 0.5 × 106 MC38 cells (day −8) and treated (n = 10 mice per group) with isotype control (133 μg, intravenously; day 2), radiation [3.6 Gray (Gy)/day; days 0 to 3], M7824 (55 μg, intravenously; day 2), or M radiation. (A) Tumor volumes, measured twice weekly. (B) Tumor weight (day 14). (C) ELISpot of IFN-γ–producing, p15E-responsive CD8+ T cells (day 14). Spleens were harvested (n = 5 mice), and CD8+ T cells were isolated. Antigen-presenting cells derived from naive splenocytes were pulsed with the KPSWFTTL (p15E) peptide or the irrelevant SIINFEKL (OVA) peptide, irradiated, and cultured with isolated CD8+ T cells. (D to F) C57BL/6 mice were inoculated intramuscularly (day −7) with 0.5 × 106 MC38 cells in the right thigh (primary tumor) and subcutaneously (s.c.) with 1 × 106 MC38 cells in the left flank (secondary tumor) and treated (n = 6 mice per group) with isotype control (400 μg; days 0, 2, and 4), radiation (5 Gy/day; days 0 to 3), M7824 (164 μg; day 0), or M radiation. Radiation was applied only to the primary tumor, as shown in (D). (E) Primary tumor volumes and (F) secondary tumor volumes were measured twice weekly. (G to I) μMt− mice were subcutaneously inoculated with 1 × 106 MC38 cells (day −7) and treated (n = 10 mice per group) with isotype control (400 μg; days 3, 6, 9, 12, and 17), M7824 (492 μg, intravenously; days 3, 6, 9, 12, and 17), oxaliplatin (Ox)/5-fluorouracil (5-FU) (5 mg/kg, intraperitoneally, and 60 mg/kg, intravenously; day 0), or M Ox/5-FU. (G) Tumor volumes were measured twice weekly. (H) Tumor weight (day 18). (I) ELISpot of IFN-γ–producing, p15E-responsive CD8+ T cells (n = 5 mice). Tumor volumes are presented as mean ± SEM. **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ denote a significant difference relative to radiation + M7824 treatment or Ox/5-FU + M7824 treatment. Tumor weights are shown for individual mice, with lines representing the means, and they were compared by unpaired t test. IFN-γ ELISpot data are means ± SEM of three replicates and were evaluated by two-way ANOVA.
Yan Lan et al., Sci Transl Med 2018;10:eaan5488
Published by AAAS