How does the tumor microenvironment play a role in hepatobiliary tumors?

The tumor microenvironment (TME) is defined as the structural and dynamic network of cellular and non-cellular interactions between malignant cells and the surrounding non-malignant matrix. Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are two of the most challenging gastrointestinal malignancies. Despite clinical advancements in understanding tumor biology and growth of the chemotherapeutic industry, there have been no corresponding improvements in prognosis and overall survival of HCC and PDAC. Both of these cancers have a very intimate relationship with their surrounding environment; the TME is thought to actively participate in initiating and sustaining these malignancies. Individual TME constituents play a vital role in chemoresistance and recurrence after surgery and have been established as independent prognostic factors. This review article will highlight the diverse structural components, key signaling pathways, and extracellular matrices of HCC and PDAC and discuss their crosstalk with tumor cells to promote growth and metastasis. The article will also summarize the latest laboratory and clinical research based on therapeutic targets identified within the TME of both HCC and PDAC.