A shift in the hepatic immunological pattern from predominant adaptive immunity to innate immunity compromises tissue-specific immunity and leads to HCC

Abstract The incidence of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) is growing because the global consumption high fat, sugar or Western diet (WD). Current data suggests a correlation between hepatic inflammation and progression NAFLD to HCC. However, contradictory reports on identification specific inflammatory cells cytokines hinder further progress in field. Such controversial are due highly reductionist approaches getting lost details. By using flow cytometry, we have demonstrated that immunological patterns were inhibition HCC, which can be discovered through detection proportion immune cell types functioning as network. cytometry utilizes limited number markers hindering comprehensive patterns. Here, perform scRNAseq collected from mouse model (DIAMOND) being WD prior after development well control mice chow (CD). We demonstrate alters pattern by dominating innate immunity, M1 macrophages, over adaptive B T cells, activation fibroblasts. Each created distinct collective function beyond its cellular constituents. Also, shifts compromised system, transforming anti-tumor carcinogenesis-promoting process. Our suggest discovery modulation could offer understanding curative treatment for This work was supported Office Assistant Secretary Defense Health Affairs Breast Cancer Research Program under Award No. W81XWH2210793. Opinions, interpretations, conclusions, recommendations those authors not necessarily endorsed U.S. Department Defense.This also supported, part, CTSA award UL1TR002649 National Center Advancing Translational Sciences.