间皮素(mesothelin)是由体腔中的间皮细胞(mesothelial cells)所产生的一种蛋白质。目前已在好几种癌症中都发现含有大量的间皮素，产生的间皮素随后进入血液循环系统中。华盛顿大学医学院的研究人员想知道是否可以通过检查血液中间皮素的水平作为判定胰腺癌的生物指标。这项研究发表在本月的Clinical Cancer Research杂志上。
胰腺癌(Pancreatic adenocarcinoma)是一种常见的癌症，美国每年约有4万人患有此类癌症。但由于该病的症状没有明显特征，往往直到癌症晚期才被诊断出来。
由于间皮素有助于肿瘤的生长，而癌细胞缺失间皮素时，癌细胞会像正常细胞一样死亡。因此，研究人员认为，如果能够利用免疫疗法敲除胰腺癌细胞的间皮素，使癌细胞像正常细胞一样会死亡，也是一种有效治疗胰腺癌的方法。
该研究表明，在所有74名胰腺癌患者中，有73名患者血液中间皮素的水平要明显高于健康人。此外还有5例患良性胰腺疾病的患者血液中胰腺癌的水平也很高。因此，也有研究人员称间皮素未必是诊断胰腺癌的有效方法。
但研究人员发现，胰腺癌患者的间皮素特异性免疫细胞可以被激活，因此，可以通过设计一种疫苗来促进对胰腺癌细胞内的间皮素的免疫应答。在这一设想成为现实之前，研究人员需要克服三重障碍：一，寻找到合适的抗原，本文中涉及的间皮素可以是其中之一；二，引入的疫苗能够引起免疫应答；三，当免疫细胞接近癌细胞时，还必须防止癌细胞关闭免疫应答。（生物谷Bioon.com）
生物谷推荐原始出处：
Clinical Cancer Research November 2009 15; 6511
Circulating Mesothelin Protein and Cellular Antimesothelin Immunity in Patients with Pancreatic Cancer
Fabian Mc. Johnston1, Marcus C.B. Tan1, Benjamin R. Tan, Jr.2, Matthew R. Porembka1, Elizabeth M. Brunt3, David C. Linehan1,4, Peter O. Simon, Jr.1, Stacey Plambeck-Suess1, Timothy J. Eberlein1,4, Karl Erik Hellstrom5, Ingegerd Hellstrom5, William G. Hawkins1,4 and Peter Goedegebuure1,4
Departments of 1Surgery, 2Internal Medicine, and 3Anatomic and Molecular Pathology, Washington University School of Medicine, and 4Siteman Cancer Center, St. Louis, Missouri; and 5Department of Pathology, Harborview Medical Center, University of Washington, Seattle, Washington
Purpose: Mesothelin is a glycoprotein expressed on normal mesothelial cells and is overexpressed in several histologic types of tumors including pancreatic adenocarcinomas. A soluble form of mesothelin has been detected in patients with ovarian cancer and malignant mesothelioma, and has prognostic value. Mesothelin has also been considered as a target for immune-based therapies. We conducted a study on the potential clinical utility of mesothelin as a biomarker for pancreatic disease and therapeutic target pancreatic cancer.
Experimental Design: Tumor cell–bound and soluble mesothelin in patients was evaluated by immunohistochemistry and ELISA, respectively. The in vitro cellular immune response to mesothelin was evaluated by INFγ ELISA and intracellular cytokine staining for IFNγ in CD4+ and CD8+ T cells. The level of circulating antibodies to mesothelin was measured by ELISA.
Results: All tumor tissue from patients with pancreatic adenocarcinoma expressed mesothelin (n = 10). Circulating mesothelin protein was detected in patients with pancreatic adenocarcinoma (73 of 74 patients) and benign pancreatic disease (5 of 5) but not in healthy individuals. Mesothelin-specific CD4+ and CD8+ T cells were generated from peripheral blood lymphocytes of patients with pancreatic cancer in 50% of patients compared with only 20% of healthy individuals. Antibodies reactive to mesothelin were detected in <3% of either patients or healthy individuals.
Conclusions: Circulating mesothelin is a useful biomarker for pancreatic disease. Furthermore, mesothelin-specific T cells can be induced in patients with pancreatic cancer. This suggests that mesothelin is a potential target for immune-based intervention strategies in pancreatic cancer.
