Systemic immune dysfunction in pancreatic cancer patients

Systemic immune dysfunction in pancreatic cancer patients
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DOI:
10.1007/s00423-006-0140-7
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发表时间:
2007-05-01
影响因子:
2.3
通讯作者:
Gansauge, Frank
Gansauge, Frank
中科院分区:
医学3区
文献类型:
--
作者:
Poch, Bertram;Lotspeich, Errki;Gansauge, Frank

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研究背景与目的采用流式细胞术检测32例胰腺癌患者外周血淋巴细胞(PBL)表面T辅助细胞(CD 4)、T抑制细胞(CD 8)、B细胞(CD 19)和NK细胞(CD 56)的表达,并与健康对照组(HC)进行比较。用刀豆蛋白A(ConA)、植物血凝素(PHA)、美洲商陆有丝分裂原(PWM)和抗CD 3抗体刺激PBL,分析PBL的胚化反应。结果PC组外周血免疫细胞分布无明显差异,但PHA或抗CD 3抗体刺激后,PC组外周血淋巴细胞(PBL)的转化反应明显降低。胰腺癌患者血清IL-2水平降低,TNF-α、TGF-β 1、IL-10、IL-2 R、IL-1 β和IL-1 RA水平显著升高。结论胰腺癌患者存在以T辅助细胞2型细胞因子为主的全身免疫功能紊乱,与T细胞抑制相关的物质显著升高,并且对PHA和PBL的抗CD 3抗体的母细胞生成反应降低。
Background and aims We investigated the immune status in 32 pancreatic cancer patients (PC) in comparison with healthy controls (HC).Materials and methods Using flow cytometry, peripheral blood lymphocytes (PBL) were characterized by the expression of surface markers for T helper cells (CD4), T suppressor cells (CD8), B cells (CD19) and NK cells (CD56). The blastogenic response of PBL was analyzed after stimulation with concavalin A (ConA), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and anti-CD3 antibodies. The serum levels of TNF-alpha, IL-1 beta, IL-2, IL-10, IL-12, IL-18, IL-1RA, sIL-2R and TGF-beta were determined by ELISA.Results No differences in the distribution of peripheral immunocytes in PC were found, whereas the blastogenic response of peripheral blood lymphocytes (PBL) after stimulation with PHA or anti-CD3 antibodies was significantly decreased in PC. In PC, we found reduced serum levels of IL-2 and significantly elevated levels of TNF-alpha, TGF-beta 1, IL-10, IL-2R, IL-1 beta and IL-1RA.Conclusion These data provide evidence for a systemic immune dysfunction in pancreatic cancer patients characterized by a shift towards a T helper cell type 2 cytokine profile, a significant elevation of substances related to T cell suppression and a reduced blastogenic response to PHA and anti-CD3 antibodies of PBL.