It will soon be possible to determine which patients with a type of liver cancer called hepatocellular carcinoma would benefit from immunotherapy, according to a study by researchers at Weill Cornell Medicine.
Posted in ‘Molecular Cell‘, the research provides new insights into two proteins, p62 and NBR1, and their opposing roles in regulating the response of a critical immune response in the liver’s fight against tumors, interferon.
Data show that high levels of NBR1, an immune system inhibitor, in these specialized cells can identify patients who are unlikely to respond to immunotherapies. On the other hand, NBR1 reduction strategies have been seen to help reduce tumor size in animal models, suggesting a possible new therapeutic approach for the subset of patients who do not respond to treatment. immunotherapy.
“p62 and NBR1 are yin and yang,” said the study’s co-principal investigator, Jorge Moscat. « Unlike NBR1, if p62 is high in hepatic stellate cells, the patient is protected against cancer, but if it is low, the immune system is affected. “If NBR1 is high, the immune system is affected, but if NBR1 is low, the immune response is increased.”
Until recently, patients with hepatocellular carcinoma had few treatment options and those that were available extended life by only a few months. Immunotherapy has offered a new alternative and can prolong your life by up to two years.
The liver is an organ that is tremendously immunosuppressed, explains María Díaz-Meco, co-principal investigator. «Reactivating the immune system is a very attractive approach that is now bearing fruit».
However, not all patients respond to immunotherapy and only a small percentage achieve long-term remission. Doctors cannot currently predict which patients will benefit. “We need biomarkers to identify which patients will respond and who will achieve long-term survival,” he says.
Previous research showed that the p62 protein, key in the immune response against hepatocellular carcinoma, is reduced in patients with this disease. The new study reveals that p62 activates STING to promote antitumor immunity, while NBR1 blocks this response by degrading STING.
Deleting NBR1 in mice restored the immune response and shrank tumors. The team seeks to develop therapies that degrade NBR1 and activate STING to improve immunotherapy and study whether eliminating NBR1 prevents metastasis and resistance to treatments.
#Biomarker #predicts #response #immunotherapy #liver #cancer
