Fig. 4
Improvement of immunotherapy efficacy when treating primary tumors with nintedanib combination therapy. a) Tumor growth in the primary EMT-6 breast cancer model. Treatment was started when average tumor volume was 120mm3, around 7 days after cell implantation. Statistical analysis on day 27. ANOVA followed by Tukey’s Multiple Comparison Test *p < 0.05, **p < 0.01. Data are presented as means ± SD, n = 6. Region of flat line in the curves means that tumor in remaining mice had regressed, and in the case of mice treated with PD-L1 antibody, tumors grew back. Mice were treated with nintedanib and/or paclitaxel (PTX) for 70 days, and then treatment stopped. b) Tumor growth in the primary EMT-6/CDDP model. Treatment was started when average tumor volume was 120mm3, 7 days after cell implantation. Statistical analysis on day 27. Kruskal-Wallis test followed by Dunn’s Multiple Comparison Test, **p < 0.01. Data are presented as means ± SD, n = 9–12. c-f) Effect of nintedanib, paclitaxel, anti-PD-L1 and the drug combinations on c) Vascularity; d) Proliferation; e) CD8+ tumor infiltrating cells; and f) Level of Necrosis. Histology and immunohistochemistry analyses were performed on tumor samples obtained from mice implanted with EMT-6/CDDP cells. Treatment was started when average tumor volume was 120mm3 and all mice were sacrificed after 10 days of treatment. The Mann-Whitney test was used for statistical analyses. Data are presented as means ± SD, n = 6–7