Walker T A, Wilson B A, Lewis A M, Cook J L
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6491-5. doi: 10.1073/pnas.88.15.6491.
The manner in which oncogenes influence tumorigenicity beyond their ability to immortalize cells is uncertain. We tested the hypothesis that, in addition to subverting cellular growth controls, oncogenes can actively determine tumor-inducing capacity by affecting neoplastic cell susceptibility to destruction by the host cellular immune response. The adenovirus type 5 E1A oncogene, which induces susceptibility to lysis by natural killer cells and encodes epitopes recognized by cytotoxic T lymphocytes, was transfected into highly tumorigenic sarcoma cells. E1A expression in these sarcoma cells eliminated their tumorigenicity in recipients with natural killer cell activity that was competent to lyse these E1A-positive targets. Thymus-dependent responses were not required for tumor rejection. These results indicate that oncogene-regulated cellular pathways that affect neoplastic cell susceptibility to natural killer cell lytic mechanisms may influence tumor development in the immunocompetent host.
癌基因影响肿瘤发生的方式，除了其使细胞永生化的能力外，尚不确定。我们测试了这样一个假说，即癌基因除了破坏细胞生长控制（机制）外，还可以通过影响肿瘤细胞对宿主细胞免疫反应破坏作用的敏感性，来积极决定肿瘤诱导能力。将5型腺病毒E1A癌基因转染至高致瘤性肉瘤细胞中，该基因可诱导对自然杀伤细胞裂解的敏感性，并编码细胞毒性T淋巴细胞识别的表位。这些肉瘤细胞中的E1A表达消除了它们在具有自然杀伤细胞活性且能够裂解这些E1A阳性靶标的受体中的致瘤性。肿瘤排斥反应不需要胸腺依赖性反应。这些结果表明，影响肿瘤细胞对自然杀伤细胞裂解机制敏感性的癌基因调控细胞途径，可能影响免疫活性宿主中的肿瘤发展。
