Belgian researchers identify how liver metastases evade immune system

Researchers in Belgium have identified a mechanism that allows metastatic cancer cells in the liver to evade the body's immune defenses, a discovery they say could help lead to new treatments for liver metastases.

The study, conducted by scientists at KU Leuven and the Flemish Institute for Biotechnology (VIB) with international collaborators, found that metastatic cancer cells exploit palmitate, a fatty acid naturally abundant in the liver, to suppress the immune system's ability to attack tumors, KU Leuven said Wednesday.

According to the researchers, cancer cells use an enzyme called DHHC17 to attach palmitate to the protein laminin-511 through a process known as palmitoylation.

The process stabilizes laminin-511, altering the behavior of nearby neutrophils -- immune cells that normally help destroy cancer cells.

Instead of attacking tumors, neutrophils exposed to laminin-511 become more likely to produce neutrophil extracellular traps (NETs), web-like structures that can promote tumor survival and the spread of cancer, the researchers said.

In experimental mouse models of liver metastasis, reducing DHHC17 activity restored the neutrophils' cancer-fighting function and significantly reduced metastatic growth.

The researchers said the effect depended on the presence of neutrophils, suggesting metastatic cancer cells use the pathway specifically to evade immune attack.

"Our findings reveal a new way in which metastatic cancer cells reshape their environment to protect themselves from immune attack," said Dr. Anke Vandekeere, first author of the study at the VIB-KU Leuven Center for Cancer Research.

"Rather than acting directly on the cancer cell alone, this pathway allows tumor cells to disarm neutrophils and undermine one of the body's natural defense mechanisms against cancer," she added.

Professor Sarah-Maria Fendt of VIB and KU Leuven said the findings could open new opportunities to develop therapies that make liver metastases more vulnerable to the immune system.