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. Author manuscript; available in PMC: 2017 Apr 1.
Published in final edited form as: Cancer Discov. 2016 Feb 19;6(4):400–413. doi: 10.1158/2159-8290.CD-15-1032

Figure 3. IFN-γ/STAT-1 signaling is necessary to redirect inflammatory monocytes with anti-fibrotic activity.

Figure 3

(A) Wild-type non-tumor bearing mice and KPC tumor-bearing mice were treated with isotype control (Ctrl) or anti-CD40 antibody. Serum was collected 24 hours after treatment for analysis. Shown are serum levels (pg/mL) of IFN-γ. n=17-20 mice per group for wild-type and n=10 mice per group for KPC. **, P<0.01; ***, P< 0.001. (B) Plasma cytokine levels were determined in PDAC patients at baseline (Pre) and 24 hours (Day +1) post treatment with the fully human CD40 agonist CP-870,893. Shown are levels (pg/mL) for IFN-γ. n=13 patients at baseline; n=5 patients after CP-870,893; **, P < 0.01; Mann-Whitney test. (C) Intracellular flow cytometry detection of pSTAT1 in murine peripheral blood leukocyte subsets one day after treatment. MFI, mean fluorescence intensity. n=5 per group, from two independent experiments; *, P<0.05, unpaired t-test. (D) Shown is pSTAT1 expression in human monocytes treated with plasma collected from PDAC patients at baseline (Pre) and multiple time points after CP-870,893 treatment. n=3; ****, P<0.0001, one-way Anova with Bonferroni correction for multiple pairwise comparison testing. (E) Representative immunofluorescence images showing co-localization of pSTAT1 in Ly6C+ inflammatory monocytes in PDAC tumors of KPC mice one day after treatment. Scale bar, 50 μm. (F) Quantification of pSTAT1 expression detected one day after treatment by immunofluorescence staining of tumor sections. n=4-5 mice per group; ****, P < 0.0001; unpaired 2-tailed t-test. (G) Quantification of extracellular matrix protein within tumors. Tumor sections were analyzed one day after treatment with control (Ctrl) or anti-CD40 antibodies with or without anti-IFN-γ antibody neutralization. n=5-9 mice per group; *, P < 0.05; **, P < 0.01; unpaired 2-tailed t-test determined from 4-6 images per mouse.