American Association for Cancer Research
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19406207capr200200-sup-242032_2_supp_6454096_qt3btt.pdf (325.42 kB)

Supplementary Figure S1 from Immune Checkpoint Inhibition is Safe and Effective for Liver Cancer Prevention in a Mouse Model of Hepatocellular Carcinoma

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journal contribution
posted on 2023-04-03, 22:12 authored by Andrew 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