title: CD13+CD4+CD25hi regulatory T cells exhibit higher suppressive function and increase with tumor stage in non-small cell lung cancer patients.
abstract: 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+CD25hiTreg cells, among CD4+CD25hiTreg 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+CD25hiTreg cells. The immune suppressive function of CD13+CD4+CD25hiTreg 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+CD25hiTreg cells. The CD13+CD4+CD25hiTreg cells also expressed higher levels of Foxp3, CTLA-4, membrane-bound transforming growth factor beta1 (mTGFbeta1) 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, mTGFbeta1 and the secretion of TGFbeta1 and IL-10 on CD13+CD4+CD25hiTreg 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+CD25hiTreg cells among the CD4+CD25hiTreg population increased significantly and correlated with pathological stage in NSCLC: healthy donor (9.84% +/- 2.23%) <stage I (21.64% +/- 2.78%) <stage II (31.86% +/- 3.01%) <stage III (45.64% +/- 6.12%) <stage IV (58.78% +/- 12.89%). Moreover, the percentage of CD13+CD4+CD25hiTreg cells decreased dramatically after surgical removal of tumors. CD13 is a new surface molecule for identifying a CD4+CD25hiTreg cell subpopulation with higher suppressive ability. The percentage of CD13+CD4+CD25hiTreg cells among the CD4+CD25hiTreg cell population correlated with the pathological stage in NSCLC and tumor burden. CD13 represents a potential target to suppress Treg cells in anti-tumor therapy.
authors: Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Songwen
authors: S
authors: Ju
authors: Hongxia
authors: H
authors: Qiu
authors: Xiaoyue
authors: X
authors: Zhou
authors: Biqin
authors: B
authors: Zhu
authors: Xin
authors: X
authors: Lv
authors: Xinen
authors: X
authors: Huang
authors: Juan
authors: J
authors: Li
authors: Yu
authors: Y
authors: Zhang
authors: Linxiang
authors: L
authors: Liu
authors: Yan
authors: Y
authors: Ge
authors: Daniel E
authors: DE
authors: Johnson
authors: Songguang
authors: S
authors: Ju
authors: Yongqian
authors: Y
authors: Shu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018826:CD13 Antigens / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D018826:CD13 Antigens