Seoul National University announced on the 23rd that Professor Lee Jung-won's research team in the College of Pharmacy has discovered a new target that can be used in the development of treatments for liver cancer. The results of this study were published in the recent issue of the international journal "Signal Transduction & Targeted Therapy."
Liver cancer has a high incidence and mortality rate, with a low five-year survival rate of 39%. While many anti-cancer drugs that suppress immune overexpression have been developed recently, their effectiveness for liver cancer, a solid tumor, remains low.
Professor Lee's research team discovered significant associations that are crucial for the growth of liver cancer cells. They anticipate that utilizing this target will enable the development of more effective anti-cancer drugs for liver cancer.
Earlier, the research team analyzed the liver cancer tissues of mice that exhibited overexpression of the membrane-penetrating protein TM4SF5 and found that the function of natural killer (NK) cells, a type of immune cell, was diminished.
The human body contains approximately 100 million NK cells, all of which develop in the liver or bone marrow. NK cells have cytotoxic functions that kill cancer cells, but when TM4SF5 is overexpressed, this function is diminished.
The research team reported that TM4SF5 overexpression and the functional decline of NK cells affect the growth of liver cancer cells and pursued further studies.
The researchers analyzed various immune checkpoints of NK cells harvested from mouse liver cancer tissues and confirmed that the expression of SLAMF7, a lymphocyte activation signaling molecule, was reduced in cells and tissues with TM4SF5 overexpression. SLAMF7 plays a role in activating NK cells to attack cancer.
The researchers analyzed that the weakening of SLAMF7's function due to TM4SF5 overexpression ultimately leads to the decreased function of NK cells.
When TM4SF5RK and SLAMF7 combine, they are sent to lysosomes, which serve as waste disposal sites within the cell, and in this process, SLAMF7 is also degraded. Therefore, the research team explained that if a compound is developed to block the binding of TM4SF5 and SLAMF7, a new liver cancer treatment could emerge with higher efficacy than existing therapies.
Professor Lee Jung-won noted, "Through this study, we have newly illuminated the interaction and targets between liver cancer cells and NK cells, and gained insights into the resulting changes in immune function," adding, "The possibility of new immune checkpoint inhibitors for effective liver cancer treatment has increased."
Reference materials
Signal Transduction & Targeted Therapy (2025), DOI: https://doi.org/10.1038/s41392-024-02106-6