title: The prevalence of FOXP3+ regulatory T-cells in peripheral blood of patients with NSCLC.
abstract: We have studied CD4(+)CD25(high)FOXP3(+) regulatory T-cells (T(regs)) from 51 patients with non-small-cell lung cancer (NSCLC) and 33 healthy donors. Regulatory T-cells were identified by fluorescence-activated cell sorting by using a panel of antibodies and by reverse transcriptase polymerase chain reaction analysis for FOXP3 expression. Functional studies were done to analyze their inhibitory role. Finally, regulatory T-cells were analyzed in malignant pleura effusion (PE) from patients with NSCLC. Patients with NSCLC have increased numbers of CD4(+)CD25(high) FOXP3(+) T(regs) in their peripheral blood and pleura effusion (PE), which express high levels of CTLA-4, GITR. These cells were anergic toward T-cell receptor stimulation and, when cocultured with activated CD4(+)CD25(-) cells, potently suppressed their proliferation and cytokine secretion. Our data suggest that in NSCLC patients, there is an increase of CD4(+)CD25(high)FOXP3(+) regulatory T-cells in the peripheral blood and tumor microenvironment. These T-cells might prevent effective antitumor immune responses, and the increase in frequency of CD4(+)CD25(high)FOXP3(+) Tregs might play a role in the modulation of the immune response against NSCLC and could be important in the design of immunotherapeutic approaches.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical School, Hua-Zhong University of Science and Technology, Wuhan, People's Republic of China. liulixiehe2004@163.com
authors.forename: Liu
authors.initials: L
authors.lastname: Li
authors.forename: Qiu Guo
authors.initials: QG
authors.lastname: Chao
authors.forename: Liu Zhong
authors.initials: LZ
authors.lastname: Ping
authors.forename: Chen
authors.initials: C
authors.lastname: Xue
authors.forename: Zhao Yan
authors.initials: ZY
authors.lastname: Xia
authors.forename: Ding
authors.initials: D
authors.lastname: Qian
authors.forename: Huang
authors.initials: H
authors.lastname: Shi-ang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001772:Blood Cell Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D060908:CTLA-4 Antigen; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000276:immunology / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma