Cancer-associated fibroblasts: Orchestrating the crosstalk between liver cancer cells and neutrophils via the CLCF1-mediated CXCL6/TGF-β axis.

Liver cancer (hepatocellular carcinoma, HCC) is one of the deadliest diseases and the 4th leading cause of cancer mortality in the world. To prolong the survival of HCC patients, immense efforts have been made to target the intrinsic key signaling pathways regulating the survival of HCC cells. However, the behaviors of cancer cells within the tumor are critically regulated by stromal cells, including fibroblasts, immune cells and endothelial cells, within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are one of the major cell populations within the TME, and activated fibroblasts are the predominant form of CAFs found in several malignancies. Specifically, in HCC, more than 80% of cases develop within the context of cirrhosis, which is always accompanied by an enrichment of activated fibroblasts due to chronic inflammation.1 Therefore, it is crucial to understand the potential crosstalk between CAFs and HCC cells.