While until now immunotherapy has shown little success against liver cancer, a new study suggests that a revamped strategy can make liver tumors highly responsive to treatment.
- Despite the progress made in recent years in the field of immunotherapies, patients affected by liver cancer respond poorly or not at all to this type of treatment. At issue: the microenvironment in which liver tumors develop.
- However, it is possible to overcome this problem by combining two treatments: an antibody commonly used in immunotherapies and a synthetic molecule that stimulates the innate immunity of the liver.
- This combination shows remarkable efficacy in inhibiting liver tumors.
For several years, immunotherapy has appeared as a promising and popular oncological approach to treat patients with advanced cancer. Its goal is to boost the immune response against tumor cells, which use several resistance strategies to neutralize and paralyze the host’s immune system. And it relies in particular on the use of antibodies called immune checkpoint inhibitors (ICI) to block cellular pathways that inhibit the activity of T lymphocytes, a type of immune system cells that help protect the body against infections and can help fight cancer.
However, despite the encouraging results of the use of immunotherapy to treat certain types of malignant tumors, many patients with liver cancer respond poorly or not at all to treatment with ICI.
However, it is possible to improve the effectiveness of immunotherapy against this cancer, as a new study shows. Published in the journal Hepatology and conducted by researchers at the University of California, San Diego, it shows that liver cancer can be made highly reactive to an immune checkpoint inhibitor known as an anti-PD antibody. -L1. This requires the use of a synthetic dsRNA molecule called polyIC to stimulate innate immunity in the liver.
Promising effects of a therapeutic combination
“There are two issues we need to keep in mind in the development of liver cancer immunotherapy, explains lead author Gen-Sheng Feng. In general, the tumor microenvironment is characterized by immune suppression, otherwise tumors will not grow. Another level of complexity is that the liver is a unique immunotolerant organ, constantly exposed to foreign substances from food. To be effective, immunotherapy must overcome hepatic immunotolerance and disrupt the immune evasion mechanism in the tumor microenvironment.”
To address these two issues, the researchers created two tumor models in mice, one with tumors growing under the skin and the other with tumors growing in the liver to study the role of different microenvironments tumours.
They then subjected the tumors to the same treatments: either the anti-PD-L1 antibody commonly used in immunotherapies, or the polyIC molecule or a combination of the two.
By comparing the responses of different tumours, they found that no monotherapy had any effect on tumors growing in the livers of mice. On the other hand, the combination of the two treatments had remarkable effects in inhibiting hepatic tumours, even better than in subcutaneous tumours.
Yes “the molecular and cellular mechanisms underlying the synergistic effect of this combination have yet to be deciphered”the study authors are enthusiastic because the first data “suggest the possibility of making liver cancer highly responsive to immunotherapy, provided a way is found to overcome the immunosuppressive environment of the liver”. “There is a promising future where patients with liver cancer can benefit from immunotherapy”they conclude.
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