It may soon be possible to determine which patients with a type of liver cancer called hepatocellular carcinoma would benefit from immunotherapy, according to a preclinical study by Weill Cornell Medicine investigators. Low NBR1 levels in hepatic stellate cells enhance interferon signaling in human hepatocellular carcinoma. Hepatic stellate cells are labeled in yellow and show reduced NBR1 expression (turquoise), whereas the strong immune response is indicated by STING staining (magenta).
The study, published Oct. 17 in Molecular Cell, provides new insights into a pair of proteins, p62 and NBR1, and their opposing functions in regulating the interferon response in hepatic stellate cells, a critical immune component in the liver’s fight against tumors. The study demonstrates that high levels of the immune-suppressing NBR1 in these specialized cells may identify patients who are unlikely to respond to immunotherapies.
It also shows that NBR1-lowering strategies help shrink tumors in animal models, suggesting a potential new therapeutic approach for the subset of patients who do not respond to immunotherapy. “P62 and NBR1 are yin and yang,” said the study’s co-principal investigator Jorge Moscat , the Homer T. Hirst III Professor of Oncology in Pathology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
“In contrast to NBR1, if p62 is high in hepatic stellate cells, a patient is protected from cancer, but if it is low, the immune syst.