Figure 5.

Effects of lurbinectedin on the tumour microenvironment of the fibrosarcoma resistant variant RES-MN/MCA1. (A) Flow cytometry analysis of circulating leukocytes of mice treated with lurbinectedin or trabectedin as detailed in the legend of Figure 3. Results are shown after one cycle of treatment. Both drugs selectively decrease the number of total monocytes (CD11b+CD115+), especially the Ly6C^high monocyte subset. (B) Flow cytometry analysis of splenic leukocytes in mice treated after three cycles. Both drugs selectively decrease the number of macrophages (CD11b+ F4/80+Ly6C^high). Statistical analysis: *P<0.05, **P<0.01 and ***P<0.001 (two-way ANOVA; Bonferroni T-test. (C) Representative immunohistochemistry pictures of tumour sections after treatment (three cycles), stained for macrophages (F4/80) or blood vessels (CD31). (D) Quantification of immunohistochemistry. Both macrophages and vessels were significantly reduced in tumours treated with lurbinectedin and trabectedin. The immunoreactive areas are calculated as mean from five microscopic fields for each sample, five mice per group. Images were analysed using Image-Pro Analyzer software. Original magnification, × 20. Statistical analysis: *P<0.05, **P<0.01 and ***P<0.001 (Student’s t-test).