Journal
CELL CYCLE
Volume 8, Issue 16, Pages 2578-2585Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.16.9302
Keywords
treg; non-small cell lung cancer; CD13; staging; aminopeptidase N
Categories
Funding
- Construction Fund for Key Medical Subjects of Jiangsu Province [XK200718]
- National Natural Science Foundation of China [30772549, 30400394]
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Regulatory T cells (Tregs) in peripheral blood and tumor infiltrating lymphocytes (TILs) play crucial roles in suppressing anti-tumor immune responses in cancer patients, and correlate with clinical outcomes. We identified an important subpopulation, CD13(+)CD4(+)CD25(hi)Treg cells, among CD4(+)CD25(hi)Treg cells in the peripheral blood of non-small cell lung cancer (NSCLC) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with NSCLC (n = 72) or from healthy donors (n = 30). Flow cytometric analyses were performed to study the expression of cell-surface or intracellular markers on the CD4(+)CD25(hi)Treg cells. The immune suppressive function of CD13(+)CD4(+)CD25(hi)Treg cells was evaluated by co-culturing with CD4(+)CD25(-)T cells that were activated by PHA. Our data showed that, compared with CD4(+)CD25(Low/-)T cells, CD13 expression was enriched on CD4(+)CD25(hi)Treg cells. The CD13(+)CD4(+)CD25(hi)Treg cells also expressed higher levels of Foxp3, CTLA-4, membrane-bound transforming growth factor beta 1 (mTGF beta 1) and B7-H1, and are more suppressive to CD25 expression and proliferation of CD4(+)CD25(-)T cells. Additionally, we showed that the expression of Foxp3, CTLA-4, B7-H1, mTGF beta 1 and the secretion of TGF beta 1 and IL-10 on CD13(+)CD4(+)CD25(hi)Treg cells was significantly suppressed by anti-CD13 mAb (WM15), and the ability of these cells to suppress CD25 expression and proliferation of CD4(+)CD25(-)T cells was inhibited by WM15 as well. Interestingly, the percentage of CD13(+)CD4(+)CD25(hi)Treg cells among the CD4(+)CD25(hi)Treg population increased significantly and correlated with pathological stage in NSCLC: healthy donor (9.84% +/- 2.23%)
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