Development of T follicular helper cells and their role in disease and immune system

Eivazi, Sadegh; Bagheri, Salman; Hashemzadeh, Mohammad Sadegh; Ghalavand, Majdedin; Qamsari, Elmira Safaie; Dorostkar, Ruhollah; Yasemi, Maryam

doi:10.1016/j.biopha.2016.10.083

Cited by 54 publications

(37 citation statements)

References 90 publications

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“…This is in accordance with previous findings that infiltrating Tfh cells were associated with prolonged OS in colorectal cancer . Tfh cells function by driving antigen‐specific B cells to selectively differentiate into memory B cells and plasma cells and by maintaining the germinal centre . Our results further support the protective roles of Tfh cells in tumors.…”

Section: Discussionsupporting

confidence: 93%

Immune infiltration in renal cell carcinoma

et al. 2019

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Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma ( RCC ). Tumor‐infiltrating immune cells ( TIIC s) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIIC s in RCC and further reveal the independent prognostic values of TIIC s. CIBERSORT , an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIIC s and immune checkpoint modulators with overall survival ( OS ). We found that CD 8+ T cells were associated with prolonged OS (hazard ratio [ HR ] = 0.09, 95% confidence interval [ CI ].01‐.53; P = 0.03) in chromophobe carcinoma ( KICH ). A higher proportion of regulatory T cells was associated with a worse outcome ( HR = 1.59, 95% CI 1.23‐.06; P < 0.01) in renal clear cell carcinoma ( KIRC ). In renal papillary cell carcinoma ( KIRP ), M1 macrophages were associated with a favorable outcome ( HR = .43, 95% CI .25‐.72; P < 0.01), while M2 macrophages indicated a worse outcome ( HR = 2.55, 95% CI 1.45‐4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA 4 and LAG 3 were associated with a poor prognosis in KIRC , and IDO 1 and PD ‐L2 were associated with a poor prognosis in KIRP . This study indicates TIIC s are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development.

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Section: Discussionsupporting

confidence: 93%

Immune infiltration in renal cell carcinoma

et al. 2019

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“…Follicular helper T cells represent a distinct CD4 + T subset that helps B cells in GC differentiate into long-lived memory B and plasma cells. [13][14][15] Studies in several tumors have shown that Tfh cells have quantitative or functional abnormalities. [25][26][27] In the present study, we investigated circulating Tfh cells in newly diagnosed NSCLC patients and identified the expansion of circulating CD4 + PD-1 + and Tfh cells, especially in those with advanced stage (III and IV).…”

Section: Discussionmentioning

confidence: 99%

“…Follicular helper T cells coexpress high levels of surface C‐X‐C motif chemokine receptor 5 (CXCR5) and inducible costimulator (ICOS), with Bcl‐6 as their distinguishing transcription factor and interleukin (IL)‐21 as their characteristic cytokine . Both peripheral circulating and germinal center (GC) Tfh cells support B‐cell activation, expansion and differentiation into plasma cells and memory B cells in GC, thereby promoting B‐cell immunity . Human circulating Tfh cells are divided into three major functional subtypes (Tfh1, Tfh2, and Tfh17), with skewing to Tfh2 and Tfh17 subtypes observed in autoimmune disease and several tumors …”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] Both peripheral circulating and germinal center (GC) Tfh cells support B-cell activation, expansion and differentiation into plasma cells and memory B cells in GC, thereby promoting B-cell immunity. [13][14][15] Human circulating Tfh cells are divided into three major functional subtypes (Tfh1, Tfh2, and Tfh17), 16 with skewing to Tfh2 and Tfh17 subtypes observed in autoimmune disease and several tumors. 17,18 Recent studies have suggested that Tfh cells and IL-21 regulate humoral immunity and cell-mediated antiviral/tumor responses in some infectious diseases and tumors.…”

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confidence: 99%

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

Qiu

Zhou

et al. 2018

Cancer Science

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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.

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“…TFH cells, a distinct subset of CD4 + T cells, specialize in providing critical assistance to germinal center (GC) B cells (5). TFH cells contribute to the generation and maintenance of GCs, support Ig class switching and assist in differentiation of GCs into memory B cells and long-lived plasma cells (6). Immune-mediated disease may occur due to the inability of TFH cells to maintain immune homeostasis (7).…”

Section: Introductionmentioning

confidence: 99%

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia

Dai

Wang

et al. 2018

Exp Ther Med

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The present study aimed to illuminate the role of circulating T follicular helper (TFH) cells in patients diagnosed with chronic immune thrombocytopenia (cITP). Fifty-four patients with cITP and 30 age-matched healthy control subjects were enrolled in the present study. TFH cell frequencies, expression of CD4+ TFH cell-associated cytokines, including interleukin (IL)-2, IL-4, IL-10 and IL-21 and associated regulatory mRNA expression levels including Bcl-6, c-Maf, Blimp-1 and PD-1 pre- and post-treatment with intravenous immunoglobulin and corticosteroids, were detected by flow cytometry, ELISA and reverse transcription-quantitative polymerase chain reaction, respectively. TFH cell frequencies of patients were significantly higher compared with healthy controls pre-treatment (P<0.05). Following treatment, significantly decreased percentages of TFH cells were present in cITP responders (P<0.05). Correlation analysis revealed that the number of TFH cells was negatively correlated with the platelet count in the peripheral blood. Furthermore, analysis of inflammatory cytokines indicated significant differences in serum interleukin (IL)-21 and IL-10 between pretreated patients and healthy controls (P<0.05). Additionally, transcription factor B-cell lymphoma (Bcl)-6, c-Maf and programmed death-ligand (PD)-1 mRNA expression levels were significantly different between cITP patients prior to treatment and the healthy controls (P<0.05). However, the expression levels of Bcl-6, C-Maf and PD-1 mRNA were significantly changed post-treatment (P<0.05). These data demonstrated that circulating TFH cells and CD4+ TFH cell-associated cytokines may serve a role in cITP. The findings suggest that the overactivation of TFH cells may contribute to the immunopathogenesis of cITP, thus blocking the pathway of TFH cells may be reasonable for therapeutic intervention.

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Development of T follicular helper cells and their role in disease and immune system

Cited by 54 publications

References 90 publications

Immune infiltration in renal cell carcinoma

Immune infiltration in renal cell carcinoma

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

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia

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Development of T follicular helper cells and their role in disease and immune system

Cited by 54 publications

References 90 publications

Immune infiltration in renal cell carcinoma

Immune infiltration in renal cell carcinoma

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

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia

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