Impaired Function of CD4+ T Follicular Helper (Tfh) Cells Associated with Hepatocellular Carcinoma Progression

Abstract

Background and AimsCD4+ 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.MethodsA 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.ResultsThe 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.ConclusionsImpairment 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.

Functionally impaired follicular helper T cells induce regulatory B cells and CD14+ human leukocyte antigen‐DR− cell differentiation in non‐small cell lung cancer

“…Gu‐Trantien et al 25 found that when Tfh cell infiltration in breast cancer patients was greater, the prognosis of patients was better. Additionally, impaired function of Tfh cells is associated with hepatocellular carcinoma progression . Thus, Tfh cells are likely to be associated with prognosis of tumor.…”

“…Additionally, impaired function of Tfh cells is associated with hepatocellular carcinoma progression. 34,35 Thus, Tfh cells are likely to be associated with prognosis of tumor. Interestingly, in the present study, we found that the number of Tfh1 subtypes was negatively correlated with disease-free survival after tumor resection, which may be related to immunosuppression induced by high PD-1 expression in Tfh1 subtypes.…”

Immunology of hepatocellular carcinoma

“…A decreased proportion of CXCR5 + CD4 + Tfh cells was found to be associated with HCC disease progression. Furthermore, these cell types were found to have an attenuated function with reduced secretion of IL21, along with the inability to promote B cell maturation, and hence were suggested to be associated with low survival rates in HCC [41] .…”

In Response to ‘The role of circulating T follicular helper cells and regulatory cells in non‐small cell lung cancer patients’

“…We read with great interest the article by Guo et al [1], which showed that increased percentage of circulating T follicular helper (cTFh) and circulating T follicular regulatory (cTFr) cells in non-small cell lung cancer (NSCLC) patients could be correlated with its pathogenesis. The role of TFh cells has been described in different types of cancers such as hepatocellular carcinoma [2] and breast cancer [3] and has also emerged as a key factor in the pathogenesis of viral-related diseases such as HBV [4].…”