Work

Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma

Year: 2022

Type: article

Abstract: Nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) represents a classic example of inflammation-linked cancer. To decipher immunological patterns associated with tumor progression or inhibition, we performed longitudinal studies in an animal model displaying gender disparity in NAFLD-associated HCC similar to humans. In response to a Western diet (WD), females and males mounted acute and chronic patterns of inflammatory cytokines, respectively. Nevertheless, tumor progression in both males and females was associated with predominant pattern of CD8+>CD4+, Th1>Th17 and M1>M2 cells in the liver. Importantly, correction of diet during NAFLD resulted in distinct hepatic immune modulation in female and male mice. In females, a balanced Th1/Th17 and M1/M2 patterns were associated with complete rescue from HCC. In males, a balanced Th1/Th17 and CD8+/CD4+ patterns were associated with partial rescue from HCC. Altogether, immunological pattern recognition and modulation should be considered for immunotherapy of HCC in a gender-specific manner.

Source: Cell Reports

DOI: 10.1016/j.celrep.2022.110454