Supplementary Figure S1 from Immune Checkpoint Inhibition is Safe and Effective for Liver Cancer Prevention in a Mouse Model of Hepatocellular Carcinoma
posted on 2023-04-03, 22:12authored byAndrew S. Chung, Marcel Mettlen, Debolina Ganguly, Tianshi Lu, Tao Wang, Rolf A. Brekken, David Hsiehchen, Hao Zhu
Neoantigens tend to increase with worsening fibrosis stage.
Funding
CPRIT
Pollack Foundation
NCI
Stand Up To Cancer Innovative Research grant
History
ARTICLE ABSTRACT
Cirrhosis is a high-risk state for hepatocellular carcinoma (HCC) development and represents an opportunity to prevent cancer. In the precancerous state of cirrhosis, there is an accumulation of neoantigens that may be specifically targetable through immunotherapy. We asked whether immune checkpoint inhibition could prevent tumorigenesis in a mouse model of diethylnitrosamine and carbon tetrachloride–induced HCC. We found that initiation of anti-PD-1 therapy prior to tumorigenesis could prevent up to 46% of liver tumors. This significant reduction in tumor burden was accompanied by infiltration of CD4+ Th cells and CD8+ cytotoxic T cells into the liver parenchyma. Importantly, anti-PD-1 therapy did not exacerbate liver dysfunction or worsen overall health in this liver disease model. Given the safety and preservation of quality of life observed with long-term immunotherapy use, an immunotherapy chemoprevention strategy is likely associated with a low risk-to-benefit ratio and high value care in select patients. These results encourage a prevention trial in cirrhotic patients with the highest risk of developing HCC.See related Spotlight by Mohammed et al., p. 897