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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 2. Anti-fibrotic activity of a CD40 agonist requires CCL2-dependent inflammatory monocyte recruitment to tumor tissue.

Figure 2

KPC mice were treated with isotype control antibody, anti-CD40, or anti-CD40 in combination with clodronate encapsulated liposomes (CEL), anti-Gr-1, anti-Ly6C or anti-CCL2. Shown are (A) representative images of PDAC sections stained with Masson's trichrome to detect extracellular matrix deposition (blue) one day after treatment and (B) quantification of extracellular matrix. n = 3-9 mice per group. Scale bar, 100 μm. (C) Quantification of Ly6C+ myeloid cells in PDAC tumors of KPC mice one day after treatment. n=3-4 mice per group. (D) Plasma CCL2 levels in PDAC patients at baseline (Pre) and 24 hours post treatment with the fully human CD40 agonist CP-870,893 n=5-13 subjects per group. Significance determined using Mann-Whitney test. (E) Serum CCL2 levels in KPC mice one day after treatment with isotype control (Ctrl) or anti-CD40 antibodies administered with or without CEL. n=7-14 mice per group. (F) Relative Ccl2 mRNA levels in PDAC implanted tumors from mice at one day after treatment. n=9-10 mice per group. (G) Ratio of peripheral blood:bone marrow F4/80+ Ly6C+ inflammatory monocytes (IM) one day after treatment. n = 4-6 mice per group. Significance testing was performed using unpaired 2-tailed Student's t test, unless otherwise specified. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.