New research shows that inflammatory macrophages can be redirected and induced to deplete fibrosis characteristic of pancreatic ductal adenocarcinoma tumors.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death, because of its tendency to cause symptoms only at a late and advanced stage. Despite our advancing knowledge of PDAC, the prognosis remains strikingly poor owing to resistance to standard therapies. The tumor stroma comprises abundant extracellular matrix (ECM) and extensive collagen, which often contribute to formation of a dense fibrosis. In addition, the tumor microenvironment is typically marked by a robust infiltrate of immunosuppressive macrophages. Together, these hallmark characteristics form a major barrier to drug delivery. Thus, strategies targeting this tumor microenvironment are necessary to improve the prognosis of PDAC patients.
Recently, researchers at the University of Pennsylvania identified a novel method to redirect macrophages to attack this tumor microenvironment . Typically, inflammatory macrophages are recruited to promote tumor growth and metastasis. Thus, some strategies have been aimed at inhibiting recruitment, depleting them in vivo, or blocking activity. In this new study, the authors found that treatment with CD40 agonists directed the mobilization of inflammatory macrophages back into peripheral blood and subsequent re-infiltration into the tumor to facilitate fibrosis degradation. CD40 agonists increase the levels of chemokine ligand 2, which facilitates macrophage infiltration of tumor tissue, and interferon gamma, which induces ECM degradation. Overall, anti-CD40 treatment resulted in depletion of PDAC stroma and induced significant tumor regression in mice following chemotherapy administration.
The findings of this study suggest that CD40 agonists could potentially enhance the efficacy of PDAC treatments. At HemaCare, we are excited to hear about new targets for cancer therapy. We are a leading provider of a variety of immune cell types, including bone marrow stem cells, monocytes, and macrophages. For more information or to place an order, call (877) 397-3087.
 Long, K. B. et al. IFNgamma and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma. Cancer discovery 6, 400-413, doi:10.1158/2159-8290.cd-15-1032 (2016).