Catholic University of Korea researchers identify liver cancer immune evasion mechanism

A research team led by Professor Nam Seok-woo at the Catholic University of Medicine has identified a new mechanism by which liver cancer cells evade immune attacks. The study reveals that abnormalities in RNA regulation within liver cancer cells can alter the function of surrounding macrophages, the innate immune cells responsible for removing abnormal cells.

The research demonstrates that an increase in the RNA-regulating protein IGF2BP2 in liver cancer cells activates MYBL2, leading to the increased expression and secretion of the HMGB2 protein. Once secreted, HMGB2 signals through the RAGE receptor on nearby macrophages, reducing their ability to engulf and eliminate cancer cells and shifting their characteristics to favor tumor survival.

The team validated these findings using genomic analysis, cell experiments, human liver cancer tissues, and animal models. Notably, inhibiting the HMGB2–RAGE signaling pathway restored the macrophages' ability to clear cancer cells. This discovery suggests that the HMGB2–RAGE pathway could serve as a new target for immunotherapy to restore anti-cancer functions in macrophages, potentially offering treatments for cancer, inflammation, and fibrosis.