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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 7. Proposed step-wise model for anti-fibrotic activity induced with a CD40 agonist in PDAC.

Figure 7

Treatment with a CD40 agonist induces the systemic release of IFN-γ which activates CCR2+ inflammatory monocytes (IM) and polarizes their phenotype toward anti-fibrotic (Step 1: Polarization). Inflammatory monocytes are then recruited to the tumor microenvironment in a CCL2-dependent manner that is regulated by resident monocytes/macrophages (RM) residing outside of the tumor microenvironment (Step 2: Trafficking). Within the tumor microenvironment, tumor infiltrating inflammatory monocytes alter the MMP profile leading to rapid degradation of extracellular matrix proteins including type I collagen and fibronectin (Step 3: Effector Activity). Together, depletion of extracellular matrix components induced by inflammatory monocytes enhances the sensitivity of tumors to gemcitabine chemotherapy.