Tumor-associated transforming growth factor-β and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients
Tumor-associated transforming growth factor-β and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients
复制标题
DOI：
10.1016/s0002-9440(10)65149-8
复制
发表时间：
1999-08-01
影响因子：
6
通讯作者：
Rodeck, U
中科院分区：
文献类型：
--
作者：
Bellone, G;Turletti, A;Rodeck, U
在这项研究中，我们报告的转化生长因子-β（TGF-β）和白细胞介素-10（IL-10）在胰腺癌组织中的共表达与胰腺癌患者血清中这两种细胞因子的水平显着升高。使用胰腺癌细胞的条件培养基（Chl），我们进一步证明肿瘤细胞衍生的TGF-β和IL-10以相加的方式抑制来自正常供体的外周血单核细胞（PBMC）制剂中的增殖和Th 1样应答的发展。胰腺癌细胞的Chl中所含的抗增殖和Th 1抑制活性主要是由于IL-10和/或TGF-β，如通过精氨酸特异性中和抗体逆转这些作用的能力所示。最后，与正常对照相比，胰腺癌患者来源的PBMC在用抗CD 3抗体或金黄色葡萄球菌菌株科万I活化后显示Th 2样细胞因子表达模式。总之，这些结果表明，胰腺肿瘤患者TGF-β和IL-10的异常产生使T细胞细胞因子产生模式偏向Th 2免疫表型。
In this study, we report coexpression of transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) in pancreatic carcinoma tissue associated with significantly elevated levels of both cytokines in the sera of pancreatic carcinoma patients. Using conditioned media (Chl) of pancreatic carcinoma cells, we further demonstrate that tumor cell-derived TGF-beta and IL-10 inhibited in an additive fashion both proliferation and the development of Th1-like responses in peripheral blood mononuclear cell (PBMC) preparations derived from normal donors. The antiproliferative and Th1-suppressive activities contained in Chl of pancreatic carcinoma cells were due primarily to IL-10 and/or TGF-beta, as shown by the capacity of cytokine-specific neutralizing antibodies to reverse these effects. Finally, as compared to normal controls, PBMC derived from pancreatic carcinoma patients displayed a Th2-like cytokine expression pattern upon activation with either anti-CD3 antibody or Staphylococcus aureus strain Cowan I. Taken together, these results suggest that aberrant production of TGF-beta and IL-10 in pancreatic tumor patients skews T-cell cytokine production patterns in favor of a Th2 immunophenotype.