Cell reports · 2022
Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma.
СтатьяПоддержка NIH: внешняя программаПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Mirshahi Faridoddin, Aqbi Hussein F, Isbell Madison, Manjili Saeed H, Guo Chunqing, Saneshaw Mulugeta, Bandyopadhyay Dipankar, Dozmorov Mikhail, Khosla Archit, Wack Katy, Carrasco-Zevallos Oscar M, Idowu Michael O, Wang Xiang-Yang, Sanyal Arun J, Manjili Masoud H
Аннотация
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.