文献类型：期刊文献

英文题名：The role of IL-36 and 37 in hepatocellular carcinoma

作者：Cao, Juan[1,2];Liu, Jun-Hong[2,3];Wise, Steven G.[4];Fan, Jingchun[5];Bao, Shisan[5];Zheng, Gui-Sen[5]

第一作者：曹娟

通信作者：Fan, JC[1];Bao, SS[1];Zheng, GS[1]

机构：[1]Gansu Univ Chinese Med, Basic Med Coll, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Dept Publ Hlth, Affiliated Hosp, Lanzhou, Peoples R China;[3]Gansu Prov Integrated Tradit Chinese & Western Med, Lanzhou, Peoples R China;[4]Univ Sydney, Fac Med & Hlth, Sch Med Sci, Sydney, NSW, Australia;[5]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Peoples R China

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Peoples R China.|[10735e9d5e7087247e71b]甘肃中医药大学公共卫生学院;[10735]甘肃中医药大学;

年份：2024

卷号：15

外文期刊名：FRONTIERS IN IMMUNOLOGY

收录：;Scopus(收录号：2-s2.0-85184112711);WOS:【SCI-EXPANDED(收录号:WOS:001154210500001)】；

基金：The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Traditional Chinese Medicine Raw Materials Quality Construction Project, (Number: 998/9983999916) for G-SZ; Provincial Key Talent Project, 2022RCXM020, Establishment and Application of Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment Model for Gastrointestinal Diseases for J-HL.

语种：英文

外文关键词：HCC; IL-36; IL-37; pathogenesis; TAM

摘要：Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.