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Publication : NAFLD indirectly impairs antigen-specific CD8<sup>+</sup> T cell immunity against liver cancer in mice.

First Author  McVey JC Year  2022
Journal  iScience Volume  25
Issue  2 Pages  103847
PubMed ID  35198900 Mgi Jnum  J:327757
Mgi Id  MGI:6885217 Doi  10.1016/j.isci.2022.103847
Citation  McVey JC, et al. (2022) NAFLD indirectly impairs antigen-specific CD8(+) T cell immunity against liver cancer in mice. iScience 25(2):103847
abstractText  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.
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