Unravelling inflammation-driven mechanisms in hepatocellular carcinoma: therapeutic targets and potential interventions

Abstract Inflammation is a key factor in the pathophysiology of hepatocellular carcinoma (HCC), one of the main causes of cancer-related death globally. The development of HCC is influenced by several immunological checkpoints and inflammatory mediators. This study concentrates on important inflammatory targets that are essential for regulating immune responses in the tumor microenvironment, such as the NOD-like receptor protein 3 (NLRP3) inflammasome, programmed cell death protein (PD-L1), stimulator of interferon genes 1 (STING1), high mobility group box 1 (HMGB1), pentraxin 1, and vascular cell adhesion molecule 1 (VCAM1). While PD-L1 inhibits anti-tumor immunity by interacting with programmed cell death protein (PD-1) on T cells, the NLRP3 inflammasome controls innate immune activation. STING1 promotes immune surveillance against tumor cells by participating in cytosolic DNA sensing. As a damage-associated molecular pattern, HMGB1 exacerbates chronic inflammation and accelerates the growth of tumors. An acute-phase protein called pentraxin 1 is involved in controlling immunological evasion and inflammatory reactions. Leukocyte recruitment and inflammation in the tumor microenvironment depend on VCAM1. Graphical Abstract