Targeting Aggressive Fibroblasts to Enhance the Treatment of Pancreatic Cancer.

INTRODUCTION

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancer entities, which is characterized by abundant desmoplastic stroma. The stroma consists of extracellular matrix, infiltrating immune cells, cancer-associated fibroblasts (CAFs) and others. Depending on environmental cues, CAFs can be highly heterogeneous and play context-dependent roles in PDAC progression.

AREAS COVERED

In this article, we discuss the biological significance of CAFs heterogeneity (oncogenic vs. tumor-suppressive) in pancreatic carcinogenesis. In particular, the complex interaction between CAFs and infiltrating immune cells has a determinant role in defining the stromal composition. A subset of PDAC patients may benefit from anti-CAFs therapy.

EXPERT OPINION

Co-defined by CAFs and infiltrating immune cells, the prognostic stroma signature is clinically relevant in a subset of human PDAC. This is the patient population which may benefit from future anti-stroma or anti-CAFs therapies. To consider CAF heterogeneity is crucial for designing anti-stroma studies. Here, reliable and traceable subtype-specific markers for CAFs are urgently needed to dissect the biological impact of CAF heterogeneity on PDAC development spatiotemporally. Given the significant contribution of CAFs to immunosuppressive microenvironment of PDAC, it is conceivable to combine anti-CAFs therapy with immunotherapy. To implement a CAF-subtype specific therapy is crucially important to improve the effectiveness of current treatments including chemotherapies and immunotherapy.