2024-10-17 15:14:00
According to a study conducted by researchers from Weill Cornell Medicine.
Posted in’Molecular cell‘, the research provides new information on 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.
The data shows 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 observed to help reduce tumor size in animal models, suggesting a possible new therapeutic approach for the subgroup of patients who do not respond to treatment. immunotherapy.
“p62 and NBR1 are yin and yang,” said the study’s co-principal investigator, Jorge Moscato. «Unlike NBR1, if p62 is high in hepatic stellate cells, the patient is protected from 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 increases.”
Until recently, hepatocellular carcinoma patients had few treatment options, and those available only extended life by a few months. Immunotherapy has offered a new alternative and can extend life by up to two years.
The liver is an extremely immunosuppressed organ, explains María Díaz-Meco, co-principal investigator. «Reactivating the immune system is a very interesting approach that is now bearing fruit».
However, not all patients respond to immunotherapy and only a small percentage achieve long-term remission. Doctors currently cannot 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 had shown that the p62 protein, fundamental in the immune response against hepatocellular carcinoma, is reduced in patients suffering from this disease. The new study reveals that p62 activates STING to promote anti-tumor immunity, while NBR1 blocks this response by degrading STING.
Deleting NBR1 in mice restored the immune response and shrank the tumors. The team seeks to develop therapies that degrade NBR1 and activate STING to improve immunotherapy and study whether deleting NBR1 prevents metastasis and treatment resistance.
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