Fig. 3: Pre-existing CD8 T cells and TIM3 on CD8+T cells is essential for the antitumour effect of TIM3-ProIL2V2.
From: TIM3-blockade synergizes with IL2 in alleviating intra-tumoral CD8+T cell exhaustion
A Female Rag1 −/− mice (n = 5/group) were inoculated with 5 × 105 MC38 cells and i.p. treated with 10 μg TIM3-ProIL2V2 on day 12 and 15 after tumor innoculation. Tumor volume was measured as indicated. B Female C57BL/6 mice (n = 6/group) were inoculated with 5 × 105 MC38 cells and i.p. treated with 10 μg TIM3-ProIL2V2 on day 14 and 17. For cell specific depletion, 500 μg anti-CSF1R or 200 μg anti-NK1.1 was administrated one day before treatment initiation and then twice a week for 2 weeks. C Female C57BL/6 mice (n = 6/group) were inoculated with 5 × 105 MC38 cells and i.p. treated with 10 μg TIM3-ProIL2V2 twice on day 14 and 17. For cell specific depletion, 200 μg anti-CD4 or anti-CD8 was administrated one day before treatment initiation and then twice a week for 2 weeks. D Female C57BL/6 mice (n = 6/group) were inoculated with 5 × 105 MC38 cells and i.p. treated with 10 μg TIM3-ProIL2V2 on day 14 and 17. FTY720 was administrated at 20 μg one day before treatment initiation and then every other day for 2 weeks. E Female Havcr2fl/fl mice, Zbtb46-Cre Havcr2fl/fl mice or Lyz2-Cre Havcr2fl/fl mice (n = 6/group) were inoculated with 5 × 105 MC38 tumor cells and i.p. treated with 10 μg TIM3-ProIL2V2 on day 14 and 17 after tumor inoculation. F Female Havcr2fl/fl mice or Cd4-Cre Havcr2fl/fl mice (n = 6/group) were inoculated with 5 × 105 MC38 tumor cells and i.p. treated with 10 μg TIM3-ProIL2V2 on day 14 and 17 after tumor inoculation. G MC38 tumor-bearing female Rag1−/− mice (n = 5/group) were transferred 1.5 × 106 Havcr3−/− CD4+T cells plus 1.5 × 106 WT CD8+T cells or 1.5 × 106 WT CD4+T cells plus 1.5 × 106 Havcr3−/− CD8+T cells 2 days after tumor inoculation. 10 μg TIM3-ProIL2V2 was administrated on day 10 and 13 after tumor inoculation. Data are shown as mean ± SEM and representative of two to three independent experiments. P value was determined by unpaired two-tailed t tests (A–D, E–G).
