Fig. 1. Loss of Gc increases CD8+ T cell dependent tumor control and augments response to immunotherapy.
(A) Growth profile of 0.2 x 106 5555 BrafV600E cancer cells implanted in separately housed groups of Gc-/- mice (n=8) and Gc+/+ littermate control mice (n=11). (B) Quantification of the indicated intratumoral immune cell populations in separately housed groups of WT C57BL/6J (n=9) or Gc-/- (n=8) mice at day 15 post-inoculation with 5555 BrafV600E cancer cells. Data are presented as number of cells per gram of tumor from two independent experiments. (C) As in (A) but mice received anti-CD8 antibody or isotype-matched control (300μg intraperitoneally (i.p.) on days -3, 1, 4, 7, 10, 13, 16, 19, 22). WT C57BL/6J + isotype (n=12), WT C57BL/6J + anti-CD8 (n=12), Gc-/- + isotype (n=14) and Gc-/- + anti-CD8 (n=13). (D) Percent of 5555 BrafV600E tumor rejection from two independent experiments in separately housed WT C57BL/6J or Gc-/- groups of mice that received anti-PD-1 monoclonal antibody or isotype-matched control (200μg i.p. every 3 days from day 3 to day 18). WT + isotype (n=15), WT + anti-PD-1 (n=16), Gc-/- + isotype (n=14), Gc-/- + anti-PD-1 (n=15). (E-F) Separately housed WT C57BL/6J or Gc-/- groups of mice implanted with 0.5 x 106 MCA-205 and given isotype-matched control or anti-CTLA-4 (50μg injected i.p. on days 6, 9 and 12). (E) Growth profile (n=10 mice per group). (F) Survival (Kaplan-Meier) curves from two independent experiments (n=21 mice per group). Data in (A, C and E) are presented as tumor volume (mm3) ± SEM and are representative of two independent experiments. Tumor growth profiles (A, C and E) were compared using Bonferroni-corrected two-way ANOVA. Groups in (B) were compared using two-tailed unpaired t test with Welch’s correction. Incidence of tumor rejection and survival (Kaplan-Meier) curves in (D and F) were compared using Log-rank (Mantel-Cox) test for comparison of each group with WT C57BL/6J + isotype and Log-rank for trend for comparison of all groups. In (F) hazard ratios (HR) with 95% confidence interval are shown in brackets, calculated as a ratio of each group / WT + isotype. *p<0.05, ***p< 0.001, ****p< 0.0001; ns, not significant.