Although deaths from cancer are declining in frequency all around the world, this has not impacted the increase in diagnosis of liver cancer as it continues to be on the rise. Because liver disease can occur as a result of alcohol, hepatitis infection, drug abuse, etc. the incidence of new diagnoses has been increasing as the number of alcoholics increases. Despite the increased incidence, the treatment for liver cancer and liver diseases is not curative and is mostly futile. However, recent data from a preclinical study offers new insight into the potential of combination immunotherapy to curb the growth and progression of liver tumors.
The research
Researchers:
UC San Diego Moores Cancer Center
Methodology:
Researchers combined two reagents, a synthetic double-stranded RNA (dsRNA) polyinosinicpolycytidylic acid (polyIC) with a programmed death-ligand 1 (PD-L1) antibody. The combination immunotherapy was administered to mice suffering from hepatocellular carcinoma.
Results:
The combination immunotherapy produced significant results by effectively halting the liver carcinoma’s development in mice with liver disease.
Conclusion:
Multiple types of research previously reported polyIC to boost the immune system’s anti-tumor activity. This immune activating ability inhibited the development and growth of liver tumors in their pre-cancer stages. However, in mice models already suffering from liver carcinoma, the polyIC had no therapeutic benefit and instead exacerbated the progression of the tumors.
Gen-Sheng Feng, Ph.D., professor of pathology and molecular biology at UC San Diego is the senior author of the paper. “Liver cancer is much more complicated than we thought,” said Feng. “We and other researchers found recently that deleting classic oncogenes ironically aggravates liver cancer. The liver has a unique immune-tolerant microenvironment. That’s why we haven’t been able to develop an effective treatment for liver cancer by blocking oncogenic signaling. Immunotherapy with checkpoint inhibitors, while in many clinical trials worldwide, may have uncertain outcomes due to low or poor response.”
How does the polyIC work to prevent liver carcinoma?
The polyIC combination immune therapy reprograms macrophages and activates natural killer cells, thereby eradicating all tumor-initiating cells.
References
Liang Wen, Bing Xin, Panyisha Wu, Chia-Hao Lin, Chuanhui Peng, Gaowei Wang, Jin Lee, Li-Fan Lu, Gen-Sheng Feng. An Efficient Combination Immunotherapy for Primary Liver Cancer by Harmonized Activation of Innate and Adaptive Immunity in Mice. Hepatology, 2019; http://dx.doi.org/10.1002/hep.30528
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