Dittmann Jasmin, Keller-Matschke Karin, Weinschenk Toni, Kratt Thomas, Heck Tobias, Becker Horst-Dieter, Stevanović Stefan, Rammensee Hans-Georg, Gouttefangeas Cécile
Department of Surgery, University Hospital, Tübingen, Germany.
Cancer Immunol Immunother. 2005 Aug;54(8):750-8. doi: 10.1007/s00262-004-0640-7. Epub 2004 Dec 22.
The tumor-associated antigens CEA, MUC1 and Her2/neu are broadly expressed in gastrointestinal tumors, and are attractive candidates for targeting by T-cell-based immunotherapy. However, little is known about the natural cytotoxic T-cell response of patients suffering from colorectal or gastric carcinoma against these three as well as other antigens. Using a quantitative reverse transcription-polymerase chain reaction-based assay for IFN-gamma, we analyzed the CD8+ T-cell repertoire present in the blood of HLA-A2+ gastrointestinal tumor survivors against five known epitopes derived from CEA, MUC1 and Her2/neu. The results show that most of the patients (16 from 22 tested) have detectable, peripheral CD8+ T cells directed against at least one of these three proteins. Interestingly, the majority of these patients reacts to the two MUC1-derived HLA-A*0201 epitopes tested (14 from 16), demonstrating that this protein represents one dominant target for CD8+ T cells in gastrointestinal cancer.
肿瘤相关抗原癌胚抗原(CEA)、粘蛋白1(MUC1)和人表皮生长因子受体2/neu(Her2/neu)在胃肠道肿瘤中广泛表达,是基于T细胞的免疫疗法的有吸引力的靶向候选物。然而,对于患有结直肠癌或胃癌的患者针对这三种以及其他抗原的天然细胞毒性T细胞反应知之甚少。我们使用基于定量逆转录-聚合酶链反应的γ干扰素检测方法,分析了HLA-A2+胃肠道肿瘤幸存者血液中针对源自CEA、MUC1和Her2/neu的五个已知表位的CD8+T细胞库。结果显示,大多数患者(22例检测患者中的16例)具有可检测到的外周CD8+T细胞,这些细胞针对这三种蛋白质中的至少一种。有趣的是,这些患者中的大多数对所检测的两个源自MUC1的HLA-A*0201表位有反应(16例中的14例),表明该蛋白是胃肠道癌中CD8+T细胞的一个主要靶点。