1. Fig. 6. Increased efficacy of immunotherapy in lymphangiogenic B16 melanomas depends on CCR7 signaling before therapy and local activation and expansion of TILs after therapy.
Increased efficacy of immunotherapy in lymphangiogenic B16 melanomas depends on CCR7 signaling before therapy and local activation and expansion of TILs after therapy. (A and B) B16-OVA/VC tumor–bearing mice treated with control IgG (Iso) or anti–VEGFR-3 (αR3)–blocking antibodies were euthanized 3 days after ATT, and tumor single-cell suspensions were analyzed by flow cytometry (n = 5). Quantification of overall naïve CD8+ (CD45+CD8+CD44−CD62L+), effector CD8+ (CD45+CD8+CD44+CD62L−), and OT-I (CD45+CD8+CD45.1+) T cells (A) in the tumor and (B) in the dLNs. (C) Tumor growth and survival curves of B16-OVA/VC tumor–bearing mice treated with anti-CCR7 (αCCR7), control IgG (Iso), or αR3 antibodies combined with ATT on day 9. CCR7 blockade was performed only before ATT (days 0, 3, and 6) (data pooled from two or more independent experiments, n ≥ 15 total). (D) Tumor growth curves of B16-OVA/VC tumor–bearing mice treated with control IgG (Iso) or αR3 antibodies received daily injections of the small molecular S1P inhibitor FTY720 starting on the same day as ATT was performed (day 9) (n ≥ 5). Statistics show differences between Iso + FTY720 and αR3 + FTY720 by one-way ANOVA. (E) Representative flow cytometry plots and (F) quantification of circulating CD4+ and CD8+ T cells (after B220 exclusion) in blood 26 days after tumor inoculation. *P < 0.05, **P < 0.01, ***P < by two-tailed Student’s t test or one-way ANOVA and log-rank (Mantel-Cox) test for survival curves.
Manuel Fankhauser et al., Sci Transl Med 2017;9:eaal4712
Published by AAAS