Haplotype loss of HLA class I antigen as an escape mechanism from immune attack in lung cancer
Haplotype loss of HLA class I antigen as an escape mechanism from immune attack in lung cancer
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DOI：
10.1158/0008-5472.can-04-3787
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发表时间：
2005-07-01
期刊：
影响因子：
11.2
通讯作者：
Yasumoto, K
中科院分区：
文献类型：
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作者：
So, T;Takenoyama, M;Yasumoto, K
肿瘤逃避宿主免疫监视系统的机制之一（即，HLA I类抗原的单倍型缺失）。我们假设大多数HLA 1类抗原表达正常的肿瘤细胞被CTL攻击和根除，只有少数HLA 1类抗原表达异常的肿瘤细胞能逃脱宿主的免疫监视系统。以YMA-1单倍型缺失的A904 L肺癌细胞株为刺激物，从自体淋巴细胞中诱导出转染的HLA-A26和HLA-B39限制性CTL细胞系。然而，仅建立了一个HLA-1339限制性CTL克隆（CTL G3 b），然后将其用于鉴定抗原。SGT 1B [SKP 1的G2等位基因的抑制子（SGT 1），动粒蛋白（SKP 1）的抑制子]被鉴定为CTL G3 b识别的抗原。使用来自A904 L原代培养物的13个亚克隆进行的进一步实验证实了我们的上述假设。因此，具有正常HLA I类表达的肿瘤细胞可以在癌发生的早期阶段被CTL杀死，并且只有具有HLA I类抗原单倍型缺失的肿瘤细胞可以逃避免疫攻击并发展成临床癌症。
One of tumor escape mechanisms from the host's immunosurveillance system (i.e., a haplotype loss of HLA class I antigens) has been detected in various tumor cells. We hypothesize that the majority of tumor cells with normal HLA class 1 expression were attacked and eradicated by CTLs, and only a minority with an abnormal expression of HLA class 1 antigens could escape the host's immunosurveillance system. Using HLA class 1-transfected tumor variants as stimulators in A904L lung cancer cell line, which has a haplotype loss of YMA class 1 antigens, both the transfected HLA-A26 and HLA-B39-restricted CTL lines were induced from autologous lymphocytes. However, only one HLA-1339-restricted CTL clone (CTL G3b) was established, and it was then used to identify the antigen. SGT1B [suppressor of G2 allele of SKP1 (SGT1), suppressor of kinetochore protein (SKP1)] was identified as the antigen recognized by CTL G3b. Further experiments using 13 subclones from a primary culture of A904L were found to confirm our above-mentioned hypothesis. Tumor cells with a normal HLA class I expression may thus be killed by CTL at an early stage of carcinogenesis, and only tumor cells with a haplotype loss of HLA class I antigens can escape an immune attack and develop into clinical cancer.