Liver could potentially help in treatment of cancer, finds study

In a study, published in Nature Immunology, researchers discovered that cancer-induced liver inflammation causes liver cells to secrete proteins called serum amyloid A proteins, which circulate through the body and hinder the ability of T cells—major anticancer weapons of the immune system—to infiltrate and attack tumors elsewhere.

Liver inflammation, a common side-effect of cancers elsewhere in the body, has long been associated with worse cancer outcomes and more recently associated with poor response to immunotherapy.

“We want to better understand what causes cancer to resist or respond to immunotherapy to help design more effective strategies for patients. Our findings show that liver cells—with their release of SAA proteins—effectively serve as an immune checkpoint regulating anti-cancer immunity, making them a promising therapeutic target,” said senior author Gregory Beatty.

In the study, researchers at the University of Pennsylvania studied mice with pancreatic cancer to see how immune cells called T cells affect tumor growth. They found that mice with fewer T cells in their tumors had more inflammation in their livers. These mice also showed increased activity in a signaling pathway related to inflammation, which the researchers previously linked to liver metastasis in another study.

To see if the results from the mouse study applied to humans, the researchers analyzed tissue samples from patients who had surgery to remove pancreatic tumors. They discovered that patients with low levels of SAA in their tissue samples during surgery tended to live significantly longer after the procedure.

“The translational findings in human patients highlight the likely clinical relevance of our discoveries in the mice. Now that we’ve shown how liver inflammation puts up a roadblock to immunotherapy, our next step is to see if the same pathway can be targeted to reverse inflammation in patients who already have liver metastasis,” said Betty.

Reference: Stone, M.L., Lee, J., Lee, J.W. et al. Hepatocytes coordinate immune evasion in cancer via release of serum amyloid A proteins. Nat Immunol (2024).