Increased CD4CD25+FOXP3+ regulatory T Cells in cancer patients from conversion of CD4+CD25- T cells through tumor-derived factors.
BACKGROUND
CD4+CD25+ regulatory T (Treg) cells play a pivotal role in the maintenance of the homeostatic balance of the immune system. The current study was conducted to evaluate the prevalence of CD4+CD25+ Treg cells in cancer patients and to identify possible mechanisms contributing to Treg cell expansion.


METHODS
The frequencies of CD4+CD25+FOXP3+ T cells in the peripheral blood mononuclear cells (PBMCs) of 62 cancer patients and 25 healthy individuals were determined by flow cytometry. The purified CD4+CD25- T cells were stimulated with malignant pleural effusion (MPE) or tumor cell-derived supernatants (TCS) from cancer patients in vitro. MPE/TCS-exposed CD4+ CD25- T cells were also characterized in terms of phenotype (CD4, CD25, and FOXP3 expression) and function (i.e. suppression assays).


RESULTS
An increased population of CD4+ CD25+FOXP3+ T cells was detected in the peripheral blood of cancer patients, with no obvious difference between the adenocarcinoma group and the squamous carcinoma group. When stimulated with MPE or TCS, a fraction of natural CD4+CD25- T cells was converted into CD4+CD25+ FOXP3+ T cells which had the functional activity resembling natural CD4+CD25+ Treg cells with anergy and imm unosuppression.


CONCLUSIONS
The percentages of CD4+CD25+ FOXP3+ Treg cells in PBMCs of cancer patients are significantly increased. Tumor-derived factors such as TGF-betamay contribute to CD4+CD25+ Treg cell expansion in cancer patients.
Mao
Chaoming
C
Department of Immunology, School of Medical Technology, Jiangsu University, Zhenjiang, PR China.
Wang
Shengjun
S
Jiang
Qian
Q
Tong
Jia
J
Ma
Jie
J
Yang
Min
M
Xu
Xiaopeng
X
Qiu
Gufeng
G
Shao
Qixiang
Q
Li
Long
L
Xu
Huaxi
H
D002450:Cell Communication / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014407:Tumor Cells, Cultured