Jerome K R, Kirk A D, Pecher G, Ferguson W W, Finn O J
Department of Laboratory Medicine, University of Washington Medical Center, Seattle 98195, USA.
Cancer Immunol Immunother. 1997 Jan;43(6):355-60. doi: 10.1007/s002620050344.
The human mucin, MUC-1, is a transmembrane glycoprotein that is produced by both normal an malignant epithelium. The MUC-1 produced by malignant epithelium is underglycosylated, which leads to the expression by tumors of novel T and B cell epitopes on the mucin polypeptide core. Similar underglycosylation occurs in the lactating breast. In this report, we describe a long-term survivor of breast cancer whose tumor strongly expressed the T- and B-cell-stimulatory epitopes. Five years after presenting with the tumor, the patient had her first pregnancy, at which time she developed fulminant lymphocytic mastitis. We demonstrate that the lactating breast produced mucin expressing the same "tumor-specific" epitopes as the original cancer. The patient had circulating anti-mucin antibodies of both the IgM and IgG isotypes (these are not found in normal controls), and mucin-specific cytotoxic T lymphocytes in the peripheral blood. Limiting-dilution analysis for mucin-specific cytotoxic T lymphocytes in three different experiments yielded frequencies of 1 in 3086, 1 in 673, and 1 in 583, compared to approximately 1 in 10(6) in normal controls. The patient remains clinically free of carcinoma after 5 additional years of follow-up. We propose that the original tumor primed the patient's immune response against the mucin epitopes, and that the re-expression of these epitopes on the lactating breast evoked a secondary immune response. It is tempting to speculate that the vigor of her anti-mucin immunity may have helped protect this patient against recurrent tumor.
人黏蛋白MUC-1是一种跨膜糖蛋白,由正常上皮细胞和恶性上皮细胞产生。恶性上皮细胞产生的MUC-1糖基化不足,这导致肿瘤在黏蛋白多肽核心上表达新的T细胞和B细胞表位。哺乳期乳腺也会出现类似的糖基化不足。在本报告中,我们描述了一位乳腺癌长期幸存者,其肿瘤强烈表达T细胞和B细胞刺激表位。肿瘤出现五年后,患者首次怀孕,此时她患上了暴发性淋巴细胞性乳腺炎。我们证明,哺乳期乳腺产生的黏蛋白表达与原发癌相同的“肿瘤特异性”表位。患者循环中存在IgM和IgG同种型的抗黏蛋白抗体(正常对照中未发现),外周血中有黏蛋白特异性细胞毒性T淋巴细胞。在三个不同实验中对黏蛋白特异性细胞毒性T淋巴细胞进行有限稀释分析,得到的频率分别为1/3086、1/673和1/583,而正常对照中约为1/10⁶。经过额外5年的随访,该患者临床上仍无癌症。我们提出,原发肿瘤启动了患者针对黏蛋白表位的免疫反应,而这些表位在哺乳期乳腺上的重新表达引发了二次免疫反应。很容易推测,她抗黏蛋白免疫的活力可能有助于保护该患者免受肿瘤复发。