Function of follicular helper T cell is impaired and correlates with survival time in non-small cell lung cancer

Ma, Qinyun; Huang, Dayu; Zhang, Huijun; Chen, Ji; Miller, Wendy A.; Chen, Xiaofeng

doi:10.1016/j.intimp.2016.10.014

Cited by 47 publications

(33 citation statements)

References 22 publications

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“…That might be the explanation of increased infiltration of Tfh cells and decreased infiltration of resting memory CD4 T cells. After cox proportional hazards regression analysis, patients with high infiltration of Tfh cells showed better clinical outcomes, which was also consistent with previous findings (Ma et al, 2016;Xu et al, 2020).…”

Section: Discussionsupporting

confidence: 91%

“…Further, benefit from immune escape, tumor cells can migrate to other space. CD4+CXCR5+ T cell population was examined to define Tfh cells (Ma et al, 2016) and PD-1+ CD4+ CXCR5+ T cells presented lower capacity to assist CD8 T cell (Ma et al, 2016). Hence, we supposed that this Tfh cell subtypes might be chosen higher infiltration so that the tumor stage and metastasis could progress.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of tobacco smoking on Tfh cells infiltration in LUSC patients has not been studied thoroughly in the past investigations. Previous studies found that Tfh cell was positively associated with OS of NSCLC (Ma et al, 2016). However, the underlying mechanism still need further exploration and in this study, we tried to explain it by the dysregulated long non-coding RNA (lncRNA)-mRNA pairs in patients with different degrees of immune cell infiltration.…”

Section: Introductionmentioning

confidence: 98%

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Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung carcinoma

Wang

Guo

2020

PeerJ

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Background Squamous cell lung carcinoma (LUSC) was closely associated with smoking which was known to have a distant immunosuppression effect. In this study, we aimed to explore the relationship between immune cells and clinical outcomes of LUSC patients with smoking history. Methods The immune cell infiltration and RNA expression profiles of LUSC patients were collected from The Cancer Genome Atlas (TCGA). Then, the correlation between immune cell infiltration and clinical characteristics was explored. According to the level of immune cell infiltration, LUSC patients with smoking history were divided into high or low group to screen the differentially expressed lncRNAs and mRNAs. The prediction of target genes was performed by miRanda. Finally, the prognostic value of a certain signature was confirmed in an independent dataset. Results Higher abundance of tumor-infiltrating T follicular helper (Tfh) cells together with a lower abundance of resting memory CD4 T cells had been found in LUSC current reformed smokers for ≤15 years and current smoking patients. Moreover, Tfh cell infiltration was not only associated with better overall survival (OS) but also varied from different degrees of TNM stage. Low expression of lncRNA PWRN1 and its potential regulating genes DMRTB1, PIRT, APOBEC1, and ZPBP2 were associated with better OS. Combining PWRN1 and four regulating genes as a signature, patients with higher-level expression of the signature had shorter survival time in not only the TCGA but also in the GEO dataset. Conclusions It was found that Tfh cells presented higher infiltration in LUSC current reformed smokers for ≤15 years and current smokers, while resting memory CD4 T cells had lower infiltration. The signature consisting of PWRN1 as well as its predicted targeted mRNAs was dysregulated in different levels of Tfh cell infiltration and might indicate patients’ OS.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung carcinoma

Wang

Guo

2020

PeerJ

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“…GC and circulating Tfh cells can stimulate the production of antibodies through the expression of IL‐10 and IL‐21 . Ma reported that Tfh cells from NSCLC patients were defective at helping naive B cells induce IgM, IgG, and IgA production. Tfh cells do not effectively produce IL‐21, which further does not effectively stimulate the production of antibodies.…”

Section: Discussionmentioning

confidence: 99%

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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“…However, B cells contribute to the formation of tertiary lymphoid structures (TLSs) - defined as accumulations of lymphocytes in proximity to the primary tumor—which are associated with better prognosis ( 99 ) (Figure 1 ). Similar to B cells, an increased presence of Tfh cells in the primary tumor site has been associated with better clinical outcomes in breast ( 106 ) and non-small cell lung carcinoma ( 107 ). High expression of molecules like CXCL-13 and IL-21 ( 106 , 108 ) by TLS associated Tfh cells contributes to the formation/organization of TLSs in the primary breast tumor and potentially contribute to the immune systems' reaction ( 109 ).…”

Section: Lymph Nodes In Neoplasmsmentioning

confidence: 99%

Lymph Node Cellular Dynamics in Cancer and HIV: What Can We Learn for the Follicular CD4 (Tfh) Cells?

Poultsidi

Dimopoulos²,

et al. 2018

Front. Immunol.

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Lymph nodes (LNs) are central in the generation of adaptive immune responses. Follicular helper CD4 T (Tfh) cells, a highly differentiated CD4 population, provide critical help for the development of antigen-specific B cell responses within the germinal center. Throughout the past decade, numerous studies have revealed the important role of Tfh cells in Human Immunodeficiency Virus (HIV) pathogenesis as well as in the development of neutralizing antibodies post-infection and post-vaccination. It has also been established that tumors influence various immune cell subsets not only in their proximity, but also in draining lymph nodes. The role of local or tumor associated lymph node Tfh cells in disease progression is emerging. Comparative studies of Tfh cells in chronic infections and cancer could therefore provide novel information with regards to their differentiation plasticity and to the mechanisms regulating their development.

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Function of follicular helper T cell is impaired and correlates with survival time in non-small cell lung cancer

Cited by 47 publications

References 22 publications

Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung carcinoma

Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung 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

Lymph Node Cellular Dynamics in Cancer and HIV: What Can We Learn for the Follicular CD4 (Tfh) Cells?

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Function of follicular helper T cell is impaired and correlates with survival time in non-small cell lung cancer

Cited by 47 publications

References 22 publications

Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung carcinoma

Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung 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

Lymph Node Cellular Dynamics in Cancer and HIV: What Can We Learn for the Follicular CD4 (Tfh) Cells?

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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