Phenotype and function of CXCR5+CD45RA-CD4+ T cells were altered in HBV-related hepatocellular carcinoma and elevated serum CXCL13 predicted better prognosis

• Published in: Oncotarget Vol. 6; no. 42; pp. 44239 - 44253
• Main Authors: Duan, Zhaojun, Gao, Jian, Zhang, Ling, Liang, Hua, Huang, Xiangbo, Xu, Qiang, Zhang, Yu, Shen, Tao, Lu, Fengmin
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 29.12.2015
• Subjects: Biomarkers, Tumor - blood; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - virology; CD4 Lymphocyte Count; Cell Differentiation; Chemokine CXCL13 - blood; Disease-Free Survival; Female; Hepatectomy; Hepatitis B - complications; Hepatitis B - virology; Humans; Immunophenotyping; Kaplan-Meier Estimate; Leukocyte Common Antigens - blood; Liver Neoplasms - blood; Liver Neoplasms - immunology; Liver Neoplasms - surgery; Liver Neoplasms - virology; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - virology; Male; Middle Aged; Neoplasm Recurrence, Local; Phenotype; Predictive Value of Tests; Proportional Hazards Models; Receptors, CXCR5 - blood; Research Paper; Risk Factors; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - virology; Time Factors; Treatment Outcome; Up-Regulation; HCC; CXCL13; HBV; T follicular helper cells; prognosis
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.6235

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.