Fig. 7. Inhibition of TGFβ signaling improves the activity of gemcitabine in Ccl3-high PDAC tumors.

A mOS of mice bearing RC416^Scr or RC416^shCcl3 orthotopic tumors treated with gemcitabine, galunisertib, their double combinations or their respective vehicles as control (n = 6). B mOS of mice bearing DT4313^NTC or DT4313^Ccl3 orthotopic tumors treated with gemcitabine, galunisertib, their double combinations, or their respective vehicles as control (n = 6). C–E Flow cytometry analysis of Cd45⁺/Cd11b⁺/F4/80⁺ TAMs (C) and their M2 (Cd45⁺/Cd11b⁺/F4/80⁺/Cd204⁺/Cd86⁻)/M1(Cd45⁺/Cd11b⁺/F4/80⁺/Cd204⁻/Cd86⁺) ratio in tumors from mice bearing RC416 (D) or DT4313 (E) cells transduced as indicated and treated for 4 weeks with gemcitabine, galunisertib, their double combinations or their respective vehicles as control (n = 4). F Plasma levels of Lif measured by ELISA in DT4313^NTC or DT4313^Ccl3 orthotopic tumors treated as indicated (n = 4). G Representative images for DT4313^NTC or DT4313^Ccl3 tumors stained with pSmad2, E-cadherin, vimentin, Gata-6, pan-Cytokeratin antibodies, and H&E. Scale bar = 60 μm. H–L Quantification of paraffin sections from orthotopic murine PDAC tumors stained as indicated in (G). Data in (C–L) are expressed as mean ± s.d. (n = 4). P values in (C–F and H–L) were calculated by one-way ANOVA and Tukey’s test. *p < 0.05; **p < 0.01; ***p < 0.001.