Chronic Inflammatory and Immune Microenvironment Promote Hepatocellular Carcinoma Evolution
Shimin Chen, Long Zhang, Yukun Chen, Xuzhi Zhang, Yi Ma
Abstract
Hepatocellular carcinoma (HCC) is among the most prevalent and dangerous cancers in the world, which is associated with hepatitis and fibrosis resulting from different etiologies, such as hepatitis B and C virus, alcohol and diabetes. Chronic inflammation is suggested to promote tumorigenesis and progression by producing inflammatory cytokines and free radicals, triggering malignant transformation of cells, promoting tumor cells proliferation and inducing tumor angiogenesis. Immunosuppressive microenvironment established in the liver also plays a vital role in HCC development. The mechanisms include activation of cancer-associated fibroblasts, upregulation of pattern recognition receptors, inhibition of effector T cells, recruitment of regulatory T cells and myeloid-derived suppressor cells, activation of hepatic stellate cells and immunosuppressive M2 macrophages. In this review, we will summarize the most recent studies and discuss the advanced mechanisms of chronic inflammatory microenvironment and immunosuppressive microenvironment promoting HCC development, aiming to explore potential therapeutic targets.