Bellone G, Turletti A, Artusio E, Mareschi K, Carbone A, Tibaudi D, Robecchi A, Emanuelli G, Rodeck U
Department of Clinical Physiopathology, University of Torino, Torino, Italy.
Am J Pathol. 1999 Aug;155(2):537-47. doi: 10.1016/s0002-9440(10)65149-8.
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 (CM) 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 CM 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.
在本研究中，我们报告了胰腺癌组织中转化生长因子-β（TGF-β）和白细胞介素-10（IL-10）的共表达，这与胰腺癌患者血清中这两种细胞因子水平的显著升高相关。利用胰腺癌细胞的条件培养基（CM），我们进一步证明肿瘤细胞来源的TGF-β和IL-10以累加方式抑制了来自正常供体的外周血单核细胞（PBMC）制剂中的增殖以及Th1样反应的发展。胰腺癌细胞CM中所含的抗增殖和Th1抑制活性主要归因于IL-10和/或TGF-β，细胞因子特异性中和抗体逆转这些效应的能力证明了这一点。最后，与正常对照相比，来自胰腺癌患者的PBMC在用抗CD3抗体或金黄色葡萄球菌考恩I株激活后呈现出Th2样细胞因子表达模式。综上所述，这些结果表明胰腺肿瘤患者中TGF-β和IL-10的异常产生使T细胞细胞因子产生模式偏向于Th2免疫表型。
