Folfirinox-dependent reprogramming of macrophages by primary pancreatic cancer CAFs

The pancreatic cancer tumor microenvironment is dominated primarily by cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs). The interecellular dialogue between CAFs and TAMs and the resulting impact on chemoresistance, specifically to Folfirinox, remains poorly understood. In this study, we sought to understand the impact of primary PDAC CAFs on macrophage reprogramming in a folfirinox-dependent manner and performed various cellular assays (viability, immunophenotyping, phagocytosis, secretory profile analysis) and transcriptomic analysis. Overall design: We established indirect cocultures, using transwell inserts, between primary pancreatic cancer (PDAC) CAFs and in vitro polarized M2 macrophages and subjected them to folfirinox treatment. Resulting macrophages were analyzed for their transcriptomic profile.