NAFLD indirectly impairs antigen-specific CD8+ T cell immunity against liver cancer in mice

John C. McVey; Benjamin L. Green; Benjamin Ruf; Justin D. McCallen; Simon Wabitsch; Varun Subramanyam; Laurence P. Diggs; Bernd Heinrich; Tim F. Greten; Chi Ma

iScience (Feb 2022)

NAFLD indirectly impairs antigen-specific CD8+ T cell immunity against liver cancer in mice

John C. McVey,
Benjamin L. Green,
Benjamin Ruf,
Justin D. McCallen,
Simon Wabitsch,
Varun Subramanyam,
Laurence P. Diggs,
Bernd Heinrich,
Tim F. Greten,
Chi Ma

Affiliations

John C. McVey: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Benjamin L. Green: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA; Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Benjamin Ruf: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA
Justin D. McCallen: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA; Brody School of Medicine, East Carolina University, Greenville, NC, USA
Simon Wabitsch: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA
Varun Subramanyam: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA
Laurence P. Diggs: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA; Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
Bernd Heinrich: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA; Department of Medicine, Hannover Medical School, Hannover, Germany
Tim F. Greten: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA; NCI CCR Liver Cancer Program, National Institutes of Health, Bethesda, MD, USA
Chi Ma: Gastrointestinal and Thoracic Malignancy Section, National Cancer Institute, National Institutes of Health, TGMB NIH/NCI/CCR Building 10 Rm 3B44 9000 Rockville Pike, Bethesda, MD, USA; Corresponding author

Journal volume & issue: Vol. 25, no. 2
p. 103847

Abstract

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Summary: Non-alcoholic fatty liver disease (NAFLD) has become an important etiology leading to liver cancer. NAFLD alters adaptive T cell immunity and has a profound influence on liver cancer development. However, it is unclear how NAFLD affects tumor antigen-specific T cell response. In this study, we generated a doxycycline-inducible MHC-I and -II antigen-expressing HCC cell line which allowed us to investigate tumor antigen-specific T cell response in two NAFLD mouse models. The system proved to be an effective and efficient way to study tumor antigen-specific T cells. Using this model, it was found that NAFLD impairs antigen-specific CD8+ T cell immunity against HCC. The effect was not due to reduced generation or intrinsic functional changes of tumor antigen-specific CD8+ T cells but caused by accumulated macrophages in the liver environment. The findings suggest that targeting macrophages in NAFLD-driven HCC may improve therapeutic outcomes.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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