The immunosuppressive tumor microenvironment in hepatocellular carcinoma-current situation and outlook

Hepatocellular carcinoma (HCC) is one of the most severe malignant tumors that threaten human health, and its incidence is still on the rise recently. In spite of the current emerging treatment strategies, the overall prognosis of liver cancer remains worrying. Currently, immunotherapy has become a new research-active spot. The emergence of immune checkpoints and targeted immune cell therapy can significantly improve the prognosis of HCC. To a large extent, the effect of this immunotherapy depends on the tumor immune microenvironment (TME), an intricate system in which cancer cells and other non-cancer cells display various interactions. Understanding the immunosuppressive situation of these cells, along with the malignant behavior of cancer cells, can assist us to design new therapeutic approaches against tumors. Therefore, it is necessary to clarify the TME of HCC for further improvement of clinical treatment. This review discussed the functions of several immunosuppressive cells and exosomes in the latest research progress of HCC, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) and tumor-associated neutrophils (TANs) interacted actively to facilitate tumor progression. It further describes the treatment methods targeting them and the potential that needs to be explored in the future.