Fig. 8. myMAFs orchestrate an immunosuppressive microenvironment in a STAT3-dependent manner in metastatic PDAC.

A Experimental design for generating metastasis bearing GFAP-STAT3 conditional knockout mice (STAT3^cKO). B Representative immunofluorescence images of immunosuppressive (Ym-1+) macrophages (F4/80+) in metastatic tumours of STAT3^WT and STAT3^cKO mice. Arrowheads indicate double-positive cells. Scale bar, 50 µm. C Quantification of F4/80+, and percentage of Ym-1 + F4/80+ cells, presented as average fold change relative to STAT3^WT. n = 6 mice per group. Error bars, SD. P value, two-way ANOVA with Tukey’s multiple comparisons. D Representative immunofluorescence images of cytotoxic (Gzmb+) T cells (CD8+) in metastatic tumours of STAT3^WT and STAT3^cKO mice. Arrowheads indicate double-positive cells. Scale bar, 50 µm. Quantification of total infiltrating (E) and cytotoxic (F) CD8+ cells, presented as average cells per field of view. N = 6 mice per group. Error bars, SD. P value, two-tailed unpaired t-test. G Experimental design for pharmacological inhibition of pSTAT3 with Silibinin (STAT3i), in Pdgfrb-GFP mice. H Representative immunofluorescence images of immunosuppressive (Ym-1+) macrophages (F4/80+) in metastatic tumours of vehicle or STAT3i-treated mice. Arrowheads indicate double-positive cells. Scale bar, 50 µm. I Quantification of F4/80+, and percentage of Ym-1 + F4/80+ cells, presented as average fold change relative to vehicle control. n = 6 mice per group. Error bars, SD. P value, two-way ANOVA with Tukey’s multiple comparisons. Quantification of total infiltrating (J) and cytotoxic (K) CD8+ cells, presented as average cells per field of view. N = 6 mice per group. Error bars, SD. P value, two-tailed unpaired t-test. L Percentage of IFNγ⁺ cells, among CD8⁺ T cells, determined by flow cytometry analysis. Data is presented as mean from n = 4 mice per group. Error bars, SD. P value, two-tailed unpaired t-test. Source data are provided as a Source Data file.