Plate J M, Shott S, Harris J E
Section of Medical Oncology, Department of Medicine, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612, USA.
Cancer Immunol Immunother. 1999 Aug;48(5):270-9. doi: 10.1007/s002620050575.
Metastatic pancreatic cancer is one of the most aggressive cancer known in man yet specific antitumor immunity has been demonstrated in lymph nodes draining the sites of pancreatic tumors. Despite this immunity, pancreatic cancer patients suffer a quick demise. To further define tumor immunity in patients with metastatic pancreatic cancer, we sought to characterize helper T cell subsets, serum cytokines, cellular cytotoxicity that is both T-cell and non-T cell mediated, as well as known tumor-derived immunosuppressive products that may be present in their peripheral blood. Significantly heightened levels of interleukin 2 (IL-2), a Th1 cytokine, were found in patients before treatment with chemotherapy while serum IL-10, a Th2 cytokine, were at significantly lower levels than observed in normal donors tested between their fifth and seventh decades of life. IL-10 levels increased progressively with age as a serum-bound protein in normal, healthy donors tested between the ages of 24 through 61. An age associated progression of increased IL-10 levels was not observed in pancreatic cancer patients. Few patients had detectable serum levels of soluble fas ligand but approximately half had elevated levels of a tumor marker, detected with the CA-15.3 assay, known as soluble MUCIN 1 (MUC1). Cell mediated cytotoxicity including T-cell mediated killing of pancreatic tumor cell lines was detected in many patients. These data suggest that pancreatic cancer patients have activated type 1 helper T cells that can support development of cell-mediated immunity, and that their sera contain lowered levels of the "anti-inflammatory" type 2 cytokine, IL-10.
转移性胰腺癌是人类已知的侵袭性最强的癌症之一，然而在引流胰腺肿瘤部位的淋巴结中已证实存在特异性抗肿瘤免疫。尽管有这种免疫反应，胰腺癌患者仍会很快死亡。为了进一步明确转移性胰腺癌患者的肿瘤免疫情况，我们试图对辅助性T细胞亚群、血清细胞因子、T细胞和非T细胞介导的细胞毒性以及外周血中可能存在的已知肿瘤源性免疫抑制产物进行特征分析。在接受化疗前的患者中发现，Th1细胞因子白细胞介素2（IL-2）水平显著升高，而Th2细胞因子血清IL-10水平显著低于50至70岁正常供体的检测值。在24至61岁的正常健康供体中，IL-10水平作为一种血清结合蛋白随年龄逐渐升高。在胰腺癌患者中未观察到与年龄相关的IL-10水平升高的进展情况。很少有患者血清中可检测到可溶性Fas配体水平，但约一半患者通过CA-15.3检测法检测到一种肿瘤标志物——可溶性粘蛋白1（MUC1）水平升高。在许多患者中检测到了包括T细胞介导的胰腺肿瘤细胞系杀伤在内的细胞介导细胞毒性。这些数据表明，胰腺癌患者具有可支持细胞介导免疫发展的活化1型辅助性T细胞，且其血清中“抗炎”型2细胞因子IL-10水平较低。
