Chronic Inflammatory and Immune Microenvironment Promote Hepatocellular Carcinoma Evolution

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.

Keywords:

• chronic inflammation
• immunosuppression
• tumor microenvironment
• hepatocellular carcinoma

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflict of interest.

Additional information

Funding

This study was supported by grants from the Natural Science Foundation of Guangdong Province (2023A1515011805 and 2022A1515011052), the National Natural Science Foundation of China (81873591), the Science and Technology Planning Project of Guangdong Province (2018A050506030), the Science and Technology Program of Guangzhou (201704020073), the Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (2013A061401007, 2017B030314018, and 2020B1212060026), and the Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation) (2015B050501002 and 2020A0505020003).