title: Impaired function of CD4+ T follicular helper (Tfh) cells associated with hepatocellular carcinoma progression.
abstract: OBJECTIVE
  CD4+ T follicular helper (Tfh) cells, a new subset of immune cells, have been demonstrated to be involved in the development and prognosis of tumors. However, their functional role in human hepatocellular carcinoma (HCC) is relatively unknown, and the detailed mechanisms in HCC development remain to be described.
  
  
  METHODS
  A total of 85 HCC patients with hepatitis B virus (HBV) infection, 25 HBV-relative liver cirrhosis (LC) patients, and 20 healthy controls (HC) were randomly enrolled. Flow cytometric analysis, immunohistochemical staining, and relative function (i.e., cytokine secretion, B cell maturation) assays were used to analyze the properties of CXCR5+CD4+ T cells. In addition, the relationship between the frequency of CXCR5+CD4+ T cells and overall survival rates or disease-free survival rates was also analyzed by the Kaplan-Meier method.
  
  
  RESULTS
  The frequency of circulating CXCR5+CD4+ T cells was significantly decreased in HCC patients compared with HBV-relative liver cirrhosis (LC) patients and healthy controls, and the decrease in circulating CXCR5+CD4+ T cells correlated with disease progression. The proportion of infiltrated CXCR5+CD4+ T cells was significantly decreased in tumor regions compared with nontumor regions. Furthermore, compared with healthy controls, the function of circulating CXCR5+CD4+ T cells in HCC was impaired, with reduced IL-21 secretion and dysfunction in promoting B cell maturation. Importantly, follow-up data indicated that a decreased frequency of circulating CXCR5+CD4+ T cells was also associated with reduced disease-free survival time in HCC patients.
  
  
  CONCLUSIONS
  Impairment of CD4+ T follicular helper cells may influence the development of HBV-associated HCC. Decreased CD4+ T follicular helper cells may represent a potential prognostic marker and serve as a novel therapeutic target for HCC patients.
authors.affiliation: Research Center for Biological Therapy, 302 Military Hospital of China-Peking University Teaching Hospital, Beijing, 100039, P. R. China.
authors.forename: Yiqiong
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, 100039, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, 100039, P. R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, 100039, P. R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, 100039, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, 100039, P. R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, 100039, P. R. China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.affiliation: Research Center for Biological Therapy, 302 Military Hospital of China-Peking University Teaching Hospital, Beijing, 100039, P. R. China; Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, 100039, P. R. China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D054380:Receptors, CXCR5 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000032:analysis; D000098546:Interleukin-21
chemical_list: D015704:CD4 Antigens; D007378:Interleukins; D054380:Receptors, CXCR5; D000509:alpha-Fetoproteins; D007371:Interferon-gamma; D000098546:Interleukin-21