Heterogeneous cancer-associated fibroblasts: A new perspective for understanding immunosuppression in pancreatic cancer.

Immunotherapy has shown promising efficacy in the treatment of a wide range of cancers; however, it has had little effect on pancreatic cancer. Cancer-associated fibroblasts (CAFs), the predominant mesenchymal cells present in the pancreatic cancer microenvironment, are powerful supporters of the malignant progression of pancreatic cancer. CAFs can modify the microenvironment, establish a refuge to aid cancer cells in immune escape by secreting large amounts of extracellular matrix, and produce soluble cytokines and exosomal vesicles. Hence, CAFs are important contributors to the failure of immunotherapy. Current in-depth studies of CAFs have shown that CAFs are a heterogeneous population of mesenchymal cells; therefore, the functional complexity of their populations needs in-depth explorations in future studies. This review summarizes how heterogeneous CAFs help cancer cells achieve immune escape and suggests potential directions for using CAFs as targets to address immune escape.