Tilkin A F, Lubin R, Soussi T, Lazar V, Janin N, Mathieu M C, Lefrère I, Carlu C, Roy M, Kayibanda M
Unité INSERM 152, Institut Cochin de Génétique Moléculaire, Paris, France.
Eur J Immunol. 1995 Jun;25(6):1765-9. doi: 10.1002/eji.1830250642.
Mutations in the p53 tumor suppressor gene are the most frequent genetic alterations found in human tumors. There are mainly point mutations that lead to single amino acid substitutions. The mutated proteins have a longer half-life than wild-type p53 and accumulate in the nucleus of tumor cells. Anti-p53 antibodies have been found in sera of patients with several types of cancers including breast cancer. This report describes a T cell immune response in three patients with breast tumors who had mutated p53 gene and accumulated p53 protein. All showed a humoral response to p53 protein and the T cells of these patients recognized the wild-type p53 protein and proliferated in response to it. The data reported here are relevant to the immune processes leading to autoimmunity and have a bearing on anti-p53 vaccine development in tumor immunology.
p53肿瘤抑制基因的突变是人类肿瘤中最常见的基因改变。主要是导致单个氨基酸替换的点突变。突变蛋白的半衰期比野生型p53长,并在肿瘤细胞核中积累。在包括乳腺癌在内的几种癌症患者的血清中发现了抗p53抗体。本报告描述了三名患有p53基因突变且p53蛋白积累的乳腺肿瘤患者的T细胞免疫反应。所有患者均对p53蛋白产生体液反应,这些患者的T细胞识别野生型p53蛋白并对其产生增殖反应。此处报告的数据与导致自身免疫的免疫过程相关,并且与肿瘤免疫学中抗p53疫苗的开发有关。