title: Phenotype and function of CXCR5+CD45RA-CD4+ T cells were altered in HBV-related hepatocellular carcinoma and elevated serum CXCL13 predicted better prognosis.
abstract: The present study reveals an immunological characterization of circulating and tumor-infiltrating T follicular helper cells (Tfh), namely CXCR5+CD45RA-CD4+ T cells, and their related cytokines in hepatitis B virus-related hepatocellular carcinoma (HCC) patients. In HCC patients, circulating Tfh cells showed a CCR7+ and/or ICOS+ phenotype with increased Th2-like cells and decreased Th1-like and Th17-like subsets. Although the bulk frequency of circulating Tfh cells was not altered in HCC patients, the frequency of infiltrated CXCR5+CD45RA-CD4+ CD3+cells was higher in tumor than in para-tumor tissues, and Th1-like cells were the predominant phenotype. Circulating Tfh cells in HCC patients were defective in the production of IL-21 in vitro, which was in accordance with lower IL-21 levels in tumor tissues than in para-tumor tissues. Serum CXCL13 was increased in HCC patients and associated with recurrence-free survival after hepatectomy. This was confirmed in an additional HCC cohort of 111 patients with up to 5 years follow-up. Immunohistochemical staining indicated that the percentage of CXCR5+ or CXCL13+ cells was higher in poorly differentiated than in well-differentiated tumors. In conclusion, patients with HBV-related HCC showed altered phenotypes and impaired function of Tfh cells or subpopulations. CXCL13 could be a potential biomarker for predicting recurrence in HCC patients after hepatectomy.
authors.affiliation: Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018791:CD4 Lymphocyte Count; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology* / Q000601:surgery / Q000821:virology; D002454:Cell Differentiation; D054382:Chemokine CXCL13 / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006509:Hepatitis B / Q000150:complications / Q000821:virology*; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D017493:Leukocyte Common Antigens / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology* / Q000601:surgery / Q000821:virology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D054380:Receptors, CXCR5 / Q000097:blood*; D012307:Risk Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D054380:Receptors, CXCR5; D017493:Leukocyte Common Antigens
keywords: CXCL13; HBV; HCC; T follicular helper cells; prognosis