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

Cell Rep. 2022 Mar 1;38(9):110454. doi: 10.1016/j.celrep.2022.110454.


To discover distinct immune responses promoting or inhibiting hepatocellular carcinoma (HCC), we perform a three-dimensional analysis of the immune cells, correlating immune cell types, interactions, and changes over time in an animal model displaying gender disparity in nonalcoholic fatty liver disease (NAFLD)-associated HCC. In response to a Western diet (WD), animals mount acute and chronic patterns of inflammatory cytokines, respectively. Tumor progression in males and females is associated with a predominant CD8+ > CD4+, Th1 > Th17 > Th2, NKT > NK, M1 > M2 pattern in the liver. A complete rescue of females from HCC is associated with an equilibrium Th1 = Th17 = Th2, NKT = NK, M1 = M2 pattern, while a partial rescue of males from HCC is associated with an equilibrium CD8+ = CD4+, NKT = NK and a semi-equilibrium Th1 = Th17 > Th2 but a sustained M1 > M2 pattern in the liver. Our data suggest that immunological pattern-recognition can explain immunobiology of HCC and guide immune modulatory interventions for the treatment of HCC in a gender-specific manner.

Keywords: DIAMOND; NASH; Th1; Th17; hepatocellular carcinoma; immunological patterns; immunotherapy; inflammation; macrophages; nonalcoholic fatty liver disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / pathology
  • Diet, Western
  • Disease Progression
  • Female
  • Liver Neoplasms* / pathology
  • Male
  • Non-alcoholic Fatty Liver Disease* / pathology