Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

Cha, Zhanshan; Qian, Guangfang; Zhang, Yan; Gu, Heng; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Bian, Qian

doi:10.1016/j.yexcr.2016.11.017

Cited by 30 publications

(27 citation statements)

References 41 publications

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“…Consistent with other models, GITR costimulation increased antigen-specific Tfh cells in TdLNs and tumor tissues. Although clinical studies have shown that the frequency of circulating Tfh cells was increased in cancer patients, the role of Tfh cells in tumor immunity has been controversial (25,43,44). In this context, we suggest that Tfh cells as antitumorigenic participants since they activated antigen-specific CD8 þ T cells.…”

Section: Discussionmentioning

confidence: 75%

“…Although the master transcription factor for Tfh cells has not been defined yet, Bcl6 is considered to be a key transcription factor for Tfh cell development (20)(21)(22). Tfh cells play a role in humoral immune responses by inducing high-affinity antibody production, but the role of Tfh cells in tumor immunity is still controversial (23)(24)(25). Although tumorinfiltrating Tfh cells are positively correlated with clinical outcome in breast cancer patients (23), IL4 produced by Tfh cells compromises antitumor immunity by driving accumulation of CD11b þ immunosuppressive myeloid cells in the tumor microenvironment, and Tfh cells have protumorigenic activity in diffuse large B-cell lymphoma (DLBCL; refs.…”

Section: Introductionmentioning

confidence: 99%

“…Although tumorinfiltrating Tfh cells are positively correlated with clinical outcome in breast cancer patients (23), IL4 produced by Tfh cells compromises antitumor immunity by driving accumulation of CD11b þ immunosuppressive myeloid cells in the tumor microenvironment, and Tfh cells have protumorigenic activity in diffuse large B-cell lymphoma (DLBCL; refs. 24,25).…”

Section: Introductionmentioning

confidence: 99%

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GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

Koh

Kim

Shin

et al. 2020

Cancer Immunology Research

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Although treatment with the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various tumor models, the underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21-producing follicular helper T (Tfh) cells play a crucial role in DTA-1-induced tumor inhibition. The administration of DTA-1 increased IL21 expression by Tfh cells in an antigen-specific manner, and this activation led to enhanced antitumor cytotoxic T lymphocyte (CTL) activity. Mice treated with an antibody that neutralizes the IL21 receptor exhibited decreased antitumor activity when treated with DTA-1. Tumor growth inhibition by DTA-1 was abrogated in Bcl6 fl/fl Cd4 Cre mice, which are genetically deficient in Tfh cells. IL4 was required for optimal induction of IL21-expressing Tfh cells by GITR costimulation, and c-Maf mediated this pathway. Thus, our findings identify GITR costimulation as an inducer of IL21-expressing Tfh cells and provide a mechanism for the antitumor activity of GITR agonism.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

Koh

Kim

Shin

et al. 2020

Cancer Immunology Research

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“…Tfr are also enriched in the lymph nodes of diffuse large B cell lymphoma (DLBCL) patients and the proportion of Tfr was reduced in patients with more advanced stage disease (85). It is unclear what the role of Tfr may be in the tumor environment but Tfh like cell infiltration has been demonstrated to be predictive of survival in breast cancer and may drive ectopic germinal centers (86).…”

Section: Tfr In Tumorsmentioning

confidence: 99%

Control of Germinal Center Responses by T-Follicular Regulatory Cells

2018

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Regulatory T-cells (Treg cells), expressing the transcription factor Foxp3, have an essential role in the control of immune homeostasis. In order to control diverse types of immune responses Treg cells must themselves show functional heterogeneity to control different types of immune responses. Recent advances have made it clear that Treg cells are able to mirror the homing capabilities of known T-helper subtypes such as Th1, Th2, Th17, and T-follicular helper cells (Tfh), allowing them to travel to the sites of inflammation and deliver suppression in situ. One of the more recent discoveries in this category is the description of T-follicular regulatory (Tfr) cells, a specialized subset of Treg cells that control Tfh and resulting antibody responses. In this review we will discuss recent advances in our understanding of Tfr biology and the role of both Tfr and activated extra-follicular Tregs (eTreg) in the control of humoral immunity.

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“…IL-21 is the major effector of cTfh cells that is critical for plasma cell generation and normal immunoglobulin production (15,16). C-X-C motif chemokine ligand (CXCL) 13 may be one of the most important factors in the homing, migration…”

Section: Introductionmentioning

confidence: 99%

Distribution of circulating follicular helper T cells and expression of interleukin‑21 and chemokine C‑X‑C ligand 13 in gastric cancer

Meng

Dong

et al. 2018

Oncol Lett

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Circulating follicular helper T (cTfh) cells are a novel subset of cluster of differentiation (CD)4+ helper T cells. Interleukin (IL)-21 and C-X-C motif chemokine ligand (CXCL)13 are the principal effectors and chemotactic regulatory factors of Tfh. However, the roles of IL-21 and CXCL13 in gastric cancer have not yet been completely elucidated. The aim of the present study was to investigate the distribution of cTfh cells, and the expression of IL-21 and CXCL13 in patients with gastric cancer was evaluated in order to ascertain the significance and potential mechanisms of these effectors in gastric cancer. A total of 50 patients with gastric cancer were enrolled as the study subjects, with 30 healthy individuals selected as controls. The percentage of cTfh cells (cTfh%) in the peripheral blood was calculated using flow cytometry. They are identified in the present study as CD4+ chemokine C-X-C receptor (CXCR)5+ inducible T cell co-stimulator (ICOS)+ cells. The serum levels of IL-21 and CXCL13 were determined by ELISA. The cTfh% in the peripheral blood and the concentration of IL-21 and CXCL13 in the serum were significantly higher in patients with gastric cancer compared with the control group. cTfh% was significantly higher in patients with lymph node metastasis, Tumor-Node-Metastasis (TNM) stage III-IV and low differentiation. The concentrations of IL-21 and CXCL13 in patients with lymph node metastasis and/or TNM III-IV were significantly higher than in those without lymph node metastasis or with TNM I-II. There was a positive correlation between cTfh%/CXCL13 and IL-21/CXCL13, while there was no correlation between cTfh%/IL-21. cTfh cells and associated factors (IL-21/CXCL13) may be involved in the development and progression of gastric cancer. There may be mutual regulation among cTfh cells, IL-21 and CXCL13.

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Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

Cited by 30 publications

References 41 publications

GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

Control of Germinal Center Responses by T-Follicular Regulatory Cells

Distribution of circulating follicular helper T cells and expression of interleukin‑21 and chemokine C‑X‑C ligand 13 in gastric cancer

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