Liver metastases are among the most difficult complications of cancer to treat, but researchers in Belgium and their international collaborators have identified a mechanism that helps metastatic cells evade one of the immune system’s most abundant defenders. The study, led by scientists at the VIB-KU Leuven Center for Cancer Research, shows that cancer cells can exploit palmitate, a fatty acid naturally abundant in the liver, to alter their surroundings and suppress the cancer-killing activity of neutrophils. Blocking this process reduced metastatic growth in experimental models, pointing to a possible new strategy for treating tumors that have spread to the liver.
The liver is a particularly favorable site for metastasis because it is metabolically active and continuously processes nutrients, including fatty acids. Cancer cells arriving in the organ encounter an environment that can provide both energy and molecular signals supporting their survival. Although scientists have increasingly recognized that tumors use local nutrients to grow, the new study examines a less understood question: how does the liver’s nutrient-rich environment influence the battle between metastatic cancer cells and immune cells?
The researchers focused on palmitate, a saturated fatty acid found naturally in the liver and used by cells in several essential biological processes. One of those processes is palmitoylation, a reversible chemical modification in which palmitate is attached to proteins. Palmitoylation can change a protein’s stability, location, or interactions with other molecules, allowing cells to fine-tune signaling pathways. In metastatic cancer cells, the team found that palmitate was attached to laminin-511 through the activity of DHHC17, an enzyme belonging to a family of palmitoyltransferases that regulate protein modification.
Laminin-511 is part of the extracellular matrix, the network of proteins surrounding cells. It helps organize tissue structure and can influence how cells move, attach, invade neighboring tissues, and establish new tumors. The researchers found that palmitoylation made laminin-511 more stable. As a result, metastatic cancer cells were able to produce a more persistent molecular environment around them, one capable of influencing nearby immune cells rather than merely supporting the physical growth and movement of the tumor.
The most important effect was observed in neutrophils. These white blood cells are best known for rapidly responding to infections, but they can also recognize and destroy cancer cells under the right conditions. Their behavior, however, is highly dependent on signals from the surrounding tissue. When exposed to laminin-511 modified by the cancer-cell palmitoylation pathway, neutrophils became less effective at attacking tumor cells. Instead, they showed an increased tendency to produce neutrophil extracellular traps, or NETs.
NETs are web-like structures made from DNA and antimicrobial proteins that neutrophils release to capture and immobilize pathogens. In cancer, however, NETs can have harmful effects. They may shield tumor cells from immune attack, support their attachment to tissues, and create conditions that promote metastatic growth. The study indicates that palmitate-driven stabilization of laminin-511 pushes neutrophils away from direct antitumor activity and toward a state that can assist the tumor.
To test whether DHHC17 was responsible for this immune suppression, the researchers manipulated the enzyme in experimental models of liver metastasis. Reducing DHHC17 activity weakened the pathway that stabilizes laminin-511 and led to smaller metastatic lesions. Crucially, the effect depended on the presence of neutrophils. This finding suggests that DHHC17 is not simply promoting cancer-cell growth in isolation; rather, metastatic cells use the enzyme and its downstream effects on laminin-511 to interfere with immune destruction.
The results reveal a form of immune evasion in which cancer cells do not need to eliminate neutrophils to benefit from them. Instead, they reshape the local molecular environment and redirect the cells’ behavior. “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,” said first author Anke Vandekeere of the VIB-KU Leuven Center for Cancer Research. The discovery adds to growing evidence that the extracellular matrix is an active participant in cancer progression, not simply a structural framework surrounding tumors.
The findings also raise the possibility that targeting palmitoylation could produce a dual therapeutic effect. Inhibiting DHHC17 or related components of the pathway might reduce tumor-promoting signals from laminin-511 while restoring the ability of neutrophils to kill metastatic cells. Such an approach would differ from strategies designed to remove neutrophils altogether. A previous clinical trial testing neutrophil depletion did not improve immunotherapy outcomes in patients with solid tumors, suggesting that reprogramming these immune cells may be more effective than eliminating them.
The study was an experimental investigation conducted in animals, so its therapeutic implications remain to be tested in human patients. Nevertheless, it offers a mechanistic explanation for how the liver’s metabolic environment can influence immune behavior during metastasis. By identifying DHHC17, palmitoylated laminin-511, and neutrophil dysfunction as connected parts of the same process, the researchers have highlighted a potential vulnerability in liver metastases. Future therapies that block this pathway could help transform neutrophils from tumor accomplices back into active defenders against metastatic cancer.
Subject of Research: Animals
Article Title: Palmitate promotes liver metastases by decreasing neutrophil antitumour behaviour
News Publication Date: 5 August 2026
Web References: https://doi.org/10.1038/s42255-026-01582-0
References: Nature Metabolism, DOI: 10.1038/s42255-026-01582-0
Keywords: Liver metastases, palmitate, palmitoylation, DHHC17, laminin-511, neutrophils, NETs, cancer immunology, immune evasion, tumor microenvironment, metastatic cancer, liver cancer research
Tags: Cancer cell immune evasionfatty acid metabolism in cancerfatty acids and immune system interactionimmune suppression by metastatic cellsliver metastasis mechanismsmetabolic influence on cancer progressionmetabolic targeting of cancer cellsneutrophil activity in cancer defensenovel therapies for metastatic cancerrole of palmitate in tumor growthstrategies to prevent liver metastasestumor microenvironment in liver
