Figure 6. Combination aRANKL and aCTLA-4 antibody administration enhances immune rejection of melanoma.
(A) Schematic of treatment regimen, in which anti-RANKL (aRANKL) or isotype control (iso) antibody was injected every other day for 11 days, followed by s.c. B16 melanoma injection (2 × 104 cells) on day 18. GVAX with or without anti-CTLA-4 (aCTLA-4) antibody was given on days 3, 6, and 10 following melanoma injection. (B) Survival curves in GVAX-treated mice receiving indicated combinations of therapy. n = 10 for each group. Mann-Whitney U test. *P < 0.05. Tumor-infiltrating lymphocytes (TIL) were harvested on day 19 following 1 × 105 B16 melanoma cell inoculation. Representative flow cytometry plots and average cumulative frequencies of Ki67+ (C) and KLRG1+ and granzyme B+ (D) among CD4+ T cells was measured. n = 9–12 in each group. One-way ANOVA and two-tailed t tests with P values adjusted using Hommel’s correction for multiple comparisons. *P < 0.05.