CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

Gu-Trantien, Chunyan; Migliori, Edoardo; Buisseret, Laurence; Wind, Alexandre de; Brohée, Sylvain; Garaud, Soizic; Noel, G. R.; Dang, Vu Luan; Lodewyckx, Jean Nicolas; Naveaux, Céline; Duvillier, Hugues; Goriely, Stanislas; Larsimont, Denis; Willard-Gallo, Karen

doi:10.1172/jci.insight.91487

Cited by 297 publications

(336 citation statements)

References 70 publications

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“…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 . Breast cancer patients with higher Tfh cell infiltrates in the tumor show better survival over those with lower Tfh cell infiltration . However, we do not know whether changes in circulating Tfh cells in NSCLC are associated with tumor development, progression and, eventually, clinical prognosis.…”

Section: Introductionmentioning

confidence: 93%

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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Section: Introductionmentioning

confidence: 93%

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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“…PD‐1 hi CXCR5 − CD4 + T cells, termed peripheral helper T cells (Tph), are expanded in rheumatoid arthritis synovium, which promote plasma cell differentiation and antibody production . Tumour‐infiltrating CXCL13‐producing CXCR5 − Tfh, called TfhX13 cells, activate antitumour humoral response in chronic inflammatory site . Our study demonstrated that PD‐1 was constituently expressed in MAIT cells from tuberculous pleural effusion.…”

Section: Discussionmentioning

confidence: 93%

“…The production of IL‐21 by Tfh is important for B cell proliferation and differentiation into plasma cells . Recently, CXCR5 − Tfh‐like cells with similar function are reported . Tumour‐infiltrating CXCL13‐producing CXCR5 − TfhX13 cells appear to promote formation of functional tertiary lymphoid structures (TLS) and activate antitumour humoral responses .…”

Section: Discussionmentioning

confidence: 99%

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Jiang

Cao

et al. 2020

Scand J Immunol

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To understand functional role of PD‐1‐expressing MAIT cells during tuberculosis infection in humans, sorted PD‐1+ and PD‐1− MAIT cells from pleural effusions of patients with pleural tuberculosis were subjected to transcriptome sequencing. PD‐1‐expressing MAIT cells were analysed by flow cytometry and their phenotypic and functional features were investigated. Transcriptome sequencing identified 144 genes that were differentially expressed between PD‐1+ and PD‐1− MAIT cells from tuberculous pleural effusions and CXCL13 was the gene with highest fold difference. The level of PD‐1‐expressing MAIT cells was associated with extent of TB infection in humans. PD‐1‐expressing MAIT cells had increased production of CXCL13 and IL‐21 as determined by flow cytometry. PD‐1highCXCR5− MAIT cells were significantly expanded in pleural effusions from patients with pleural tuberculosis as compared with those from peripheral blood of both patients with tuberculosis and healthy controls. Although PD‐1highCXCR5− MAIT cells from tuberculous pleural effusions had reduced IFN‐γ level and increased expression of Tim‐3 and GITR, they showed activated phenotype and had higher glucose uptake and lipid content. It is concluded that PD‐1‐expressing MAIT cells had reduced IFN‐γ level but increased production of both CXCL13 and IL‐21.

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“…In particular, it has been described that the infiltration of CXCL13‐producing Tfh cells within the intratumor tertiary lymphoid structures associates to a better clinical outcome in patients with breast cancer . A high CXCL13 signature has also been demonstrated to be a convincing marker of better prognosis in ovarian and colon cancer .…”

Section: Cancer: New Insightsmentioning

confidence: 99%

“…69 In particular, it has been described that the infiltration of CXCL13producing Tfh cells within the intratumor tertiary lymphoid structures associates to a better clinical outcome in patients with breast cancer. 43,93 A high CXCL13 signature has also been demonstrated to be a convincing marker of better prognosis in ovarian and colon cancer. 94 Consistently, an improved antitumor immune response has been associated with the presence of highly organized lymphoid structures including HEVs in both animal models and patients affected by colorectal carcinoma.…”

Section: Cancer: New Insightsmentioning

confidence: 99%

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

Nerviani

Pitzalis

2018

Journal of Leukocyte Biology

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Ectopic (or tertiary) lymphoid structures (ELS) are organized aggregates of lymphocytes resembling secondary lymphoid organs and developing in chronically inflamed nonlymphoid tissues during persistent infections, graft rejection, autoimmune conditions, and cancer. In this review, we will first depict the mechanisms regulating ELS generation, focusing on the role played by lymphoid chemokines. We will then characterize ELS forming in target organs during autoimmune conditions, here exemplified by rheumatoid arthritis, and cancer, highlighting the relevance of the tissue‐specific factors. Finally, we will discuss the clinical significance of ELS and the therapeutic potential of their inhibition and/or enhancement depending on the disease considered.

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CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

Cited by 297 publications

References 70 publications

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

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

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

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CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

Cited by 297 publications

References 70 publications

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

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

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

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Product

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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

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