Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions

作     者：Abdel-Rahman N Zekri Somaya El Deeb Abeer A Bahnassy Abeer M Badr Mona S Abdellateif Gamal Esmat Hosny Salama Marwa Mohanad Ahmed Esam El-dien Shimaa Rabah Assmaa Abd Elkader 

作者机构：Molecular Virology and Immunology UnitDepartment of Cancer BiologyNational Cancer InstituteCairo University Department of ZoologyFaculty of ScienceCairo University Department of PathologyNational Cancer InstituteCairo University Medical Biochemistry and Molecular BiologyDepartment of Cancer BiologyNational Cancer InstituteCairo University Department of Hepatology and Tropical MedicineFaculty of MedicineCairo University Department of BiochemistryMisr University for Science and Technology 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2018年第24卷第11期

页      面：1228-1238页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

主　　题：Hepatocellular carcinoma Hepatitis C virus NKG2D CD40 interleukin-2 interleukin-10 myeloid dendritic cells plasmacytoid cells natural killer cell Cytokines 

摘      要：AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P 0.01,P 0.001 and P 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.