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Cited by 29Cancer Immunotherapy and BiomarkersHepatocellular Carcinoma Treatment and PrognosisHepatitis B Virus Studies

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

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Chung, Andrew S., Mettlen, Marcel, Ganguly, Debolina, Lu, Tianshi, Wang, Tao, Brekken, Rolf A., Hsiehchen, David, Zhu, Hao·2020·Cancer Prevention Research
DOI 10.1158/1940-6207.capr-20-0200PMC PMC8284815

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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

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  • Many murine liver cancer models enforce oncogene or tumor suppressor perturbations in all hepatocytes or use mutagens that humans are rarely exposed to.

    “Because many murine liver cancer models enforce oncogene or tumor suppressor perturbations in all hepatocytes or use mutagens that humans are rarely exposed to (20, 21), one cannot solely depend on these models to identify the cell of origin or to track the evolution of HCCs.”

    From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [21]

    The Discussion (page not available) says that commonly used mouse models rely on tumor-suppressor deletion or oncogene activation, while the Results describe a model using DEN to induce mutagenesis. The paper does not say that the genetic perturbations occur in all hepatocytes or that humans are rarely exposed to the mutagens used. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Chung, A. S., Mettlen, M., Ganguly, D., Lu, T., Wang, T., Brekken, R. A., Hsiehchen, D., & Zhu, H.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Zhu, Hao
ORCID
Venue
Cancer Prevention Research
Publisher
American Association for Cancer Research (AACR)
Published
2020-11-01
Volume
13
Issue
11
Pages
911-922
ISSN
  • 1940-6207 (ISSN-L)
  • 1940-6215
DOI
10.1158/1940-6207.capr-20-0200
PMC
PMC8284815
OpenAlex
W3081025330
Cited by
29
References
3
Citations by year
2026: 2 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 1
FWCI
1.72
Type
journal article
Language
en
Open access
Locations
  • Cancer Prevention Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • CPRIT (RP190208)
  • Pollack Foundation
  • NCI (R01 CA251928)
  • Stand Up To Cancer Innovative Research grant (SU2C-AACR-IRG 10-16)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
Keywords
immune checkpoint blockade, hepatocellular carcinoma, liver cancer prevention, liver cirrhosis, anti-PD-1 therapy, chemoprevention, diethylnitrosamine, carbon tetrachloride, tumor immunology, CD8+ cytotoxic T lymphocytes, CD4+ T cells, tumor burden, immunotherapy safety
MeSH terms
Immune Checkpoint Inhibitors, Animals, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Quality of Life, Mice, Programmed Cell Death 1 Receptor

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