Immune checkpoint inhibition is safe and effective for liver cancer prevention in a mouse model of hepatocellular carcinoma

Andrew S. Chung, Marcel Mettlen, Debolina Ganguly, Tianshi Lu, Tao Wang, Rolf A. Brekken, David Hsiehchen, Hao Zhu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 target-able 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 CD4þ Th cells and CD8þ 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.

Original languageEnglish (US)
Pages (from-to)911-922
Number of pages12
JournalCancer Prevention Research
Volume13
Issue number11
DOIs
StatePublished - Nov 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Immune checkpoint inhibition is safe and effective for liver cancer prevention in a mouse model of hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this