Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA.
Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA; VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA; College of Science, Mustansiriyah University, Baghdad, Iraq.
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.
为了发现促进或抑制肝细胞癌（HCC）的独特免疫反应，我们对免疫细胞进行了三维分析，将动物模型中不同性别之间非酒精性脂肪性肝病（NAFLD）相关 HCC 的免疫细胞类型、相互作用以及随时间的变化进行了关联。在对西方饮食（WD）的反应中，动物分别产生急性和慢性炎症细胞因子模式。在男性和女性中，肿瘤的进展与肝脏中占主导地位的 CD8 CD4、Th1 > Th17 > Th2、NKT > NK、M1 > M2 模式相关。女性完全免受 HCC 的影响与 Th1 = Th17 = Th2、NKT = NK、M1 = M2 模式的平衡相关，而男性部分免受 HCC 的影响与 CD8 = CD4、NKT = NK 的平衡以及 Th1 = Th17 > Th2 的半平衡相关，但 M1 > M2 模式在肝脏中持续存在。我们的数据表明，免疫模式识别可以解释 HCC 的免疫生物学，并以性别特异性的方式指导免疫调节干预治疗 HCC。
