Expressions and significance of B7-H1 and PD-1 in peripheral blood immune cells from patients with bladder cancer
-
摘要: 目的:研究膀胱癌患者外周血中树突状细胞(dendritic cells, DCs)表面B7-H1和CD8+T淋巴细胞表面PD-1的表达情况及其临床意义。方法:分离30例膀胱癌患者外周血单个核细胞(peripheral blood mononuclear cell, PBMC),联合培养后采用流式细胞术检测DCs表面B7-H1及CD8+T细胞表面PD-1的表达情况。结果:膀胱癌患者外周血DCs表面B7-H1表达水平及CD8+T细胞表面PD-1表达水平均明显高于正常人,差异具有显著统计学意义(P<0.01),并且二者的表达水平随着病理分级和临床分期的增加均升高,差异有统计学意义(P<0.05)。结论:在膀胱癌发生发展过程中存在着DCs表面B7-H1和CD8+T细胞表面PD-1分子表达的上调,B7-H1/PD-1信号通路可能在T细胞免疫应答的初始阶段亦参与了膀胱癌免疫逃逸的发生。Abstract: Objective: To study the expressions and the clinical significance of B7-H1 on dendritic cell and PD-1 on CD8+T lymphocytes cells in peripheral blood from patients with bladder cancer.Methods: Peripheral blood mononuclear cell were disparted from 30 bladder cancer patients and 10 healthy controls by density gradient centrifugation and then co-cultured. The expressions of B7-H1 on dendritic cells (DCs) and PD-1 on CD8+T lymphocytes were analyzed by flow cytometry.Results: Expressions of B7-H1 on dendritic cells and PD-1 on CD8+T lymphocytes in bladder cancer were higher than healthy controls (P<0.01). And the expressions were strongly associated with the pathological grade and clinical stage of bladder cancer (P<0.05).Conclusions: The upregulation of B7-H1 on DCs and PD-1 on CD8+T lymphocytes were strongly associated with neoplastic progression of bladder cancer. B7-H1/PD-1 signal passway may also play an important role in immune escape of bladder cancer during initial phase of T cell immune response.
-
Key words:
- bladder cancer /
- B7-H1 /
- PD-1 /
- dendritic cells /
- CD8+t lymphocytes /
- immune escape
-
-
[1] Chemnitz J M, Parry R V, Nichols K E, et al. SHP-1 and SHP-2 associate with immunoreceptor ryrosine-based switch motif of programmed death-1 upon primary T cell stimulation,but only receptor ligation prevents T cell activation[J]. J Immunol, 2004, 173(2):945-954.
[2] Fife B T, Guleria I, Gubbels Bupp M, et al. Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1[J]. J Exp Med, 2006, 203:2737-2747.
[3] Tsushima F, Yao S, Shin T, et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy[J]. Blood, 2007, 110:180-185.
[4] Gajewski T F, Meng Y, Harlin H, et al. Immune suppression in the tumor microenvironment[J]. J Immunother, 2006, 29(3):233-240.
[5] Dong H, Strome S E, Salomao D R, et al. Tumor-associated B7-H1 promotes T-cell apoptosis:a potential mechanism of immune evasion[J]. Nat Med, 2002, 8(8):793-800.
[6] Keir M E, Butte M J, Freeman G J, et al. PD-1 and its ligands in tolerance and immunity[J]. Annu Rev Immunol, 2008, 26:677-704.
[7] Freeman G J, Long A J, Iwai Y, et al. Engagement of the PD-1 immuninhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation[J]. J Exp Med, 2000, 192(7):1027-1034.
[8] Seo S K,Seo H M, Jeong H Y, et al. Co-inhibitory role of t cell associated B7-H1 and B7-DC in the T-cell immune response[J]. Immunol Lett, 2006, 1 02(2):222-228.
[9] Hinrichs C S, Spolski R, Paulos C M, et al. IL-2 and IL-24 confer-opposing differentiation programs to CD8+T cells for sdoptive immunotherapy[J]. Blood, 2008, 111(11):5326-5333.
[10] 王永华. 共刺激分子B7-H1和FasL在膀胱移行细胞癌免疫逃逸中的机制研究及临床意义[J]. 临床泌尿外科杂志, 2008, 23(9):684-686.
[11] Qian Y, Deng J, Geng L, et al. TLR4 signaling induces B7-H1 expression through MAPK pathways in bladder cancer cells[J]. Cancer Invest, 2008, 26(8):816-821.
-
计量
- 文章访问数: 37
- PDF下载数: 57
- 施引文献: 0