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  4. Regulatory T Cells Suppress Natural Killer Cell Immunity in Patients with Human Cervical Carcinoma
 
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Regulatory T Cells Suppress Natural Killer Cell Immunity in Patients with Human Cervical Carcinoma

Journal
International Journal of Gynecological Cancer
Journal Volume
26
Journal Issue
1
Pages
156-162
Date Issued
2016
Author(s)
WEN-CHUN CHANG  
Li C.-H.
Chu L.-H.
Huang P.-S.
BOR-CHING SHEU  
Huang S.-C.
DOI
10.1097/IGC.0000000000000578
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84953228781&doi=10.1097%2fIGC.0000000000000578&partnerID=40&md5=f200e685a9d9680531613130e328b3f4
https://scholars.lib.ntu.edu.tw/handle/123456789/546057
Abstract
Objective To determine the functional attributes of CD4+ CD25+ regulatory T (Treg) cells by suppressing natural killer (NK) cell activity in human cervical cancer (CC). Methods Triple-color flow cytometry was used to study the phenotypic expression of CD4+ CD25+ Treg cells and NK cells in the peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs). In vitro coculture assays were performed to illustrate the cytokine immunoregulations between Treg cells and NK cells. Results Significantly lower expression ratio of NK cells and higher expression ratio of Treg cells in TILs than PBLs were found. The NK cells displayed significantly higher expression ratio of inhibitory NK receptors (CD158a, CD158b, and NKG2A) and lower expression ratio of activating NK receptors (NKG2D, NKp46, and NKp30) as well as perforin in TILs than PBLs, suggesting the suppressed cytotoxicity of the NK cells in the CC tumor milieu. The expression ratio of transforming growth factor-β1 (TGF-β1) on Treg cells as well as TGF-βRII on Treg cells and NK cells was significantly higher in TILs than PBLs. Further functional in vitro assays demonstrated that NK cell function was suppressed by Treg cells, mimicking the inhibition of TGF-β on NK cells, and interleukin-2/interleukin-15 stimulation was able to restore the NK cell activity. Conclusions These findings indicate that Treg cells in TILs may abrogate NK cell cytotoxicity through TGF-β pathway, and therefore, Treg cell elimination may enhance NK cell activity and be a novel therapeutic strategy for CC. ? 2015 by IGCS AND ESGO.
SDGs

[SDGs]SDG3

Other Subjects
CD16 antigen; CD3 antigen; CD4 antigen; CD56 antigen; interleukin 12; interleukin 15; interleukin 2; interleukin 2 receptor alpha; killer cell immunoglobulin like receptor 2DL1; natural cytotoxicity triggering receptor 1; natural cytotoxicity triggering receptor 3; natural killer cell receptor; natural killer cell receptor NKG2A; natural killer cell receptor NKG2D; perforin; transforming growth factor beta receptor 2; transforming growth factor beta1; leukocyte antigen; transforming growth factor beta1; CD4+ CD25+ T lymphocyte; cell activity; cell assay; cellular immunity; clinical article; coculture; Conference Paper; controlled study; cytotoxicity; female; flow cytometry; human; human cell; immunoregulation; immunostimulation; in vitro study; natural killer cell; peripheral lymphocyte; phenotype; priority journal; protein expression; regulatory T lymphocyte; tumor associated leukocyte; tumor immunity; uterine cervix carcinoma; adenocarcinoma; CD8+ T lymphocyte; follow up; immunology; lymphocyte activation; metabolism; natural killer cell; prospective study; regulatory T lymphocyte; squamous cell carcinoma; uterine cervix tumor; Adenocarcinoma; Antigens, CD; Carcinoma, Squamous Cell; CD8-Positive T-Lymphocytes; Female; Flow Cytometry; Follow-Up Studies; Humans; Killer Cells, Natural; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Prospective Studies; T-Lymphocytes, Regulatory; Transforming Growth Factor beta1; Uterine Cervical Neoplasms
Publisher
Lippincott Williams and Wilkins
Type
conference paper

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