Non‐small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide, as it typically displays irreversible progression and poor prognosis. Interaction between programmed death 1 (PD‐1) and its ligand, PD‐L1, plays important roles in tumor immunology. Follicular helper T (Tfh) cells have characteristically high PD‐1 expression; thus, in the present study, we investigated the role of circulating Tfh cells and their correlation with disease‐free survival after tumor resection in NSCLC. We found significantly higher number of Tfh cells but lower serum interleukin (IL)‐21 levels in NSCLC patients, especially in those with advanced stage (III and IV), indicating that the function of Tfh cells to produce IL‐21 was impaired. Further analysis showed that the increase in Tfh cells was attributable to an expansion of the PD‐1+‐Tfh2 and PD‐1+‐Tfh17 subtypes. Functional analysis showed that Tfh cells from NSCLC patients induced the differentiation of regulatory B cells and CD14+ human leukocyte antigen (HLA)‐DR
− cells. Interestingly, the number of Tfh1 subtypes in NSCLC patients was negatively correlated with disease‐free survival after tumor resection. In short, the high number and abnormal function of Tfh cells could cause further immunosuppression and lead to tumor development in NSCLC. Rescuing Tfh functions therefore represents a potential therapeutic strategy in NSCLC.
Follicular CXCR5 + CD8 + T cells have antiviral effects in chronic virus infection, but the roles of these cells during dengue virus 2 (DENV2) infection remain poorly understood. Objective: This study was conducted to analyzed in detail the dynamic changes and functional properties of circulating follicular CXCR5 + CD8 + T cells to explore their effects on DENV2 infection. Methods: Circulating follicular CXCR5 + CD8 + T cells and cytokines were analyzed by flow cytometry in DENV2 patients at difference days after DENV2 infection. CD8 + T cells were isolated and purified from DENV2 patients, then were stimulated with NS1 peptides and TCR stimulant. After cultivation, multiple parameters were tested. Results: (1) CXCR5 + CD8 + T cells emerged after DENV2 infection, with high PD-1 expression, and were correlated with the reduction in DENV2 RNA viral loads. (2) PD-1 + CXCR5 + CD8 + T cells were negatively associated with disease progression. (3) Serum IFN-g, IL-6 and IL-10 levels were increased late in the course of DENV2 infection. (4) CXCR5 + CD8 + T cells from DENV2 patients exhibited increased cytotoxicity and IFN-g and IL-10 secretion. Conclusion: CXCR5 + CD8 + T cells could play a protective role in dengue pathogenesis and may be a novel strategy for controlling DENV2 infection and vaccine development.
Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression. Our findings revealed the expansion of circulating CD4CXCR5, CD4ICOS, CD4PD-1 and CD4CXCR5ICOSPD-1 (Tfh) cells but lower serum IL-21 levels and CD4 T cell polarization not only to Tfh2 subtypes but also to Tfh17 subtypes in patients with CLL at pretreatment compared to patients with monoclonal B cell lymphocytosis (MBL) and healthy individuals, especially in those with advanced stage, which indicate these Tfh cells could be employed as a novel indicator for disease progression. Moreover, we observed significant correlations of Tfh17 and immunoglobulin heavy chain variable region (IGHV) mutation. Importantly, significantly decreased CD4ICOS, CD4PD-1 and Tfh cells were found after effective treatments, whereas a significantly high CD4ICOS, CD4PD-1 and Tfh cells were still found in those with progressive disease after treatments, suggesting that circulating CD4ICOS, CD4PD-1, Tfh cells could predict therapeutic effects.
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