Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients
Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients
复制标题
DOI：
10.1158/1078-0432.ccr-04-2304
复制
发表时间：
2005-05-15
影响因子：
11.5
通讯作者：
Pastan, I
中科院分区：
文献类型：
--
作者：
Ho, M;Hassan, R;Pastan, I
目的：间皮素是存在于细胞表面的糖基-磷脂酰肌醇锚定的糖蛋白。间皮素是在间皮瘤、卵巢癌和胰腺癌上高度表达的分化抗原。人类对间皮素的自发体液免疫应答的存在尚未得到充分研究。在这里，我们解决的问题，是否间皮素elyphin的体液免疫反应在间皮瘤和卵巢cancer.Experimental设计：使用ELISA，我们分析了免疫球蛋白G抗体特异性间皮瘤和上皮性卵巢癌患者血清中的间皮素。结果：39.1%的间皮瘤患者血清中检测到高水平的间皮素特异性抗体（69例患者中的27例）和41.7%的上皮性卵巢癌与正常对照人群（44名献血员;间皮瘤和卵巢癌均P < 0.01）相比，24名患者中有10名患者发生了卵巢癌。我们还发现，53%至56%的间皮素免疫染色阳性间皮瘤和卵巢癌患者具有间皮素特异性抗体，而只有0%至8%的间皮素免疫染色阴性患者可检测到间皮素特异性抗体（X-2检验：间皮瘤P < 0.01，卵巢癌P = 0.025）。我们的研究结果表明间皮素是间皮瘤和卵巢癌患者的一种新的肿瘤抗原，间皮素的免疫原性与其在肿瘤细胞上的高表达有关。间皮素是基于免疫的治疗的一个很好的靶点。
Purpose: Mesothelin is a glycosyl-phosphaticlylinositol - anchored glycoprotein present on the cell surface. Mesothelin is a differentiation antigen that is highly expressed on mesothelioma, ovarian cancer, and pancreatic cancer. The existence of a spontaneous humoral immune response to mesothelin in humans has not been fully studied. Here we addressed the issue of whether mesothelin elicits a humoral immune response in patients with mesothelioma and ovarian cancer.Experimental Design: Using an ELISA, we analyzed immunoglobulin G antibodies specific for mesothelin in sera from patients with mesothelioma and epithelial ovarian cancer. Tumor specimens were examined by immunohistochemistry for mesothelin protein expression.Results: Elevated levels of mesothelin-specific antibodies were detected in the sera of 39.1% of patients with mesothelioma (27 of 69 patients) and 41.7% with epithelial ovarian cancer (10 of 24 patients) when compared with a normal control population (44 blood donors; P < 0.01 for both mesothblioma and ovarian cancer). We also found that 53% to 56% of patients with mesothelin immunostaining-positive mesothelioma and ovarian cancer had antibodies specific for mesothelin, whereas only 0% to 8% of patients with negative mesothelin immunostaining had detectable mesothelin-specific antibodies (X-2 test: P < 0.01 for mesothelioma and P = 0.025 for ovarian cancer).Conclusions: Our findings indicate that mesothelin is a new tumor antigen in patients with mesotheliom and ovarian cancer and the immunogenicity of mesothelin is associated with its high expression on the tumor cells. Mesothelin represents an excellent target for immunebased therapies.