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. |