Lipid metabolism in the immune niche of tumor-prone liver microenvironment
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AbstractThe liver is not only a common primary site for tumorigenesis, but also cancer metastasis. Advanced cancer patients with liver metastases also show reduced response rates and survival benefits when treated with immune checkpoint inhibitors. Accumulating evidence has highlighted the importance of the liver immune microenvironment in determining tumorigenesis, metastasis-organotropism as well as immunotherapy resistance. Various immune cells such as T cells, natural killer and natural killer T cells, macrophages and dendritic cells, as well as stromal cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells and hepatocytes are implicated in contributing to the immune niche of tumor-prone liver microenvironment. In parallel, as the major organ for lipid metabolism, the increased abundance of lipids and their metabolites are linked to processes crucial for non-alcoholic fatty liver disease (NAFLD) and related liver cancer development. Furthermore, the proliferation, differentiation and functions of hepatic immune and stromal cells are also reported to be regulated by lipid metabolism. Therefore, targeting lipid metabolism may hold great potential to reprogram the immunosuppressive liver microenvironment and synergistically enhance the immunotherapy efficacy in the circumstance of liver metastasis. In this review, we describe how the hepatic microenvironment adapts to the lipid metabolic alterations in pathologic conditions like NAFLD. We also illustrate how these immunometabolic alterations promote the development of liver cancers and immunotherapy resistance. Finally, we discuss the current therapeutic options and hypothetic combination immunotherapies for the treatment of advanced liver cancers.
All Author(s) ListJintian CHEN, Thomas T.H. CHAN, Jingying ZHOU
Journal nameJournal of Leukocyte Biology
Volume Number115
Issue Number1
PublisherOxford University Press
Pages68 - 84
LanguagesEnglish-United Kingdom
KeywordsNAFLD, hepatocellular carcinoma, immunotherapy resistance, lipid metabolism, liver immune microenvironment, liver

Last updated on 2024-29-02 at 09:20