間皮素(mesothelin)是由體腔中的間皮細(xì)胞(mesothelial cells)所產(chǎn)生的一種蛋白質(zhì),。目前已在好幾種癌癥中都發(fā)現(xiàn)含有大量的間皮素,，產(chǎn)生的間皮素隨后進(jìn)入血液循環(huán)系統(tǒng)中,。華盛頓大學(xué)醫(yī)學(xué)院的研究人員想知道是否可以通過檢查血液中間皮素的水平作為判定胰腺癌的生物指標(biāo),。這項(xiàng)研究發(fā)表在本月的Clinical Cancer Research雜志上,。
胰腺癌(Pancreatic adenocarcinoma)是一種常見的癌癥,，美國每年約有4萬人患有此類癌癥。但由于該病的癥狀沒有明顯特征,，往往直到癌癥晚期才被診斷出來,。
由于間皮素有助于腫瘤的生長，而癌細(xì)胞缺失間皮素時(shí),，癌細(xì)胞會(huì)像正常細(xì)胞一樣死亡,。因此，研究人員認(rèn)為,，如果能夠利用免疫療法敲除胰腺癌細(xì)胞的間皮素,，使癌細(xì)胞像正常細(xì)胞一樣會(huì)死亡，也是一種有效治療胰腺癌的方法,。
該研究表明,，在所有74名胰腺癌患者中，有73名患者血液中間皮素的水平要明顯高于健康人,。此外還有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，也有研究人員稱間皮素未必是診斷胰腺癌的有效方法,。
但研究人員發(fā)現(xiàn),，胰腺癌患者的間皮素特異性免疫細(xì)胞可以被激活，因此,，可以通過設(shè)計(jì)一種疫苗來促進(jìn)對胰腺癌細(xì)胞內(nèi)的間皮素的免疫應(yīng)答,。在這一設(shè)想成為現(xiàn)實(shí)之前，研究人員需要克服三重障礙：一,，尋找到合適的抗原,，本文中涉及的間皮素可以是其中之一；二,，引入的疫苗能夠引起免疫應(yīng)答,；三，當(dāng)免疫細(xì)胞接近癌細(xì)胞時(shí),，還必須防止癌細(xì)胞關(guān)閉免疫應(yīng)答,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
