Tanaka K, Gorelik E, Watanabe M, Hozumi N, Jay G
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892.
Mol Cell Biol. 1988 Apr;8(4):1857-61. doi: 10.1128/mcb.8.4.1857-1861.1988.
Transfection of a functional major histocompatibility complex class I gene into certain tumor cells, induced by oncogenic viruses or chemical carcinogens, can effectively abrogate their tumorigenic activity. Since experimentally induced tumors possess strong tumor-specific transplantation antigens, expression of cell surface class I antigens may present the tumor cells to appropriate immune effector cells. Most spontaneously arising tumors do not possess tumor-specific transplantation antigens, and their tumorigenicity may not be affected by the expression of a transfected class I gene. We demonstrate that the poorly immunogenic B16-BL6 melanoma can be rendered nontumorigenic in syngeneic mice by the expression of the class I H-2K antigen but not the class II I-A antigen. Furthermore, the poorly tumorigenic, class I-expressing B16-BL6-transfected cells can effectively immunize syngeneic C57BL/6 mice against the highly tumorigenic, class I-deficient B16-BL6 parental cells. Our success in experimentally manipulating the tumorigenicity of a spontaneously derived neoplasm offers hope for a potential modality for the effective treatment of human cancer.
将功能性主要组织相容性复合体I类基因转染到由致癌病毒或化学致癌物诱导产生的某些肿瘤细胞中,可有效消除其致瘤活性。由于实验诱导的肿瘤具有强大的肿瘤特异性移植抗原,细胞表面I类抗原的表达可能会将肿瘤细胞呈递给合适的免疫效应细胞。大多数自发产生的肿瘤不具有肿瘤特异性移植抗原,其致瘤性可能不受转染的I类基因表达的影响。我们证明,免疫原性较差的B16-BL6黑色素瘤通过表达I类H-2K抗原而非II类I-A抗原,可在同基因小鼠中变得无致瘤性。此外,致瘤性较差、表达I类的B16-BL6转染细胞可有效免疫同基因C57BL/6小鼠,使其抵抗致瘤性强、缺乏I类的B16-BL6亲本细胞。我们在实验中成功操控自发产生的肿瘤的致瘤性,为有效治疗人类癌症的潜在方法带来了希望。