Frequency of MAGE-3 gene expression in HLA-A2 positive patients with non-small cell lung cancer
Frequency of MAGE-3 gene expression in HLA-A2 positive patients with non-small cell lung cancer
复制标题
DOI：
10.1016/s0169-5002(98)00017-8
复制
发表时间：
1998-05-01
期刊：
影响因子：
5.3
通讯作者：
Mitsudomi, T
中科院分区：
文献类型：
--
作者：
Gotoh, K;Yatabe, Y;Mitsudomi, T
黑色素瘤抗原MAGE-1和MAGE-3分别存在于人类白细胞抗原-A1和-Cw*1601，或-A1和-A2上，分别被提呈给相应的细胞毒性T淋巴细胞(CTL)。如果在患者体内产生了识别这些抗原的CTL，阳性肿瘤细胞的克隆应该被消除。为了确定这种免疫反应在肺癌患者中是否活跃，并确定肺癌患者中有多少适合进行MAGE定向免疫治疗，我们评估了肺癌患者肿瘤中人类白细胞抗原-AI或-A2的表达与MAGE-1或-3基因表达的关系。逆转录-聚合酶链式反应(RT-PCR)检测MAGE-1和MAGE-3分别为18/55(33%)和23/55(42%)。等位基因特异性聚合酶链式反应显示，在我们的队列中，分别有0/55(0%)和22/55(40%)的人表达了HLA-A1和-A2等位基因。在22例人类白细胞抗原-A携带者中？免疫组织化学检测到的HLAI类抗原有5例(23%)缺失。HLA-A2组MAGE-3的表达频率为5/17(29%)，略低于未表达组的18/38(47%)，但差异无统计学意义(P=0.17)。HLAA2/MAGE-3共表达与生存期无明显相关性(P=0.15，Logank检验)。我们的结论是，没有确凿的证据可以消除共表达人类白细胞抗原-A？的肺癌。和体内的MAGE-3。大约10%(5/55)的日本肺癌患者是基于MAGE-3的免疫治疗的潜在候选者。(C)1998爱思唯尔爱尔兰科学有限公司。保留所有权利。
Melanoma tumor antigens, MAGE-1 and -3 are presented on HLA-A1 and -Cw*1601, or -A1 and -A2, respectively, to the corresponding cytotoxic T lymphocytes (CTL). If CTL recognizing these antigens were generated in patients, clones of positive tumor cells should be eliminated. To ascertain whether such an immunological response is active in patients with lung cancer and to determine what fraction of lung cancer patients are candidates for MAGE oriented immunotherapy, we assessed the relationship between HLA-AI or -A2 expression and MAGE-1 or -3 gene expression in their tumors. MAGE-1 and -3 were detected in 18/55 (33%) and 23/55 (42%), respectively, by reverse transcriptase (RT)-polymerase chain reaction (PCR). Allele specific PCR revealed HLA-A1 and -A2 alleles to be expressed in 0/55 (0%) and 22/55 (40%) of our cohort, respectively. Among the 22 patients with HLA-A? genotype, expression of HLA class I antigens detectable by immunohistochemistry was lost in five (23%) cases. The frequency of MAGE-3 expression in HLA-A2 patients was 5/17 (29%), somewhat lower than that of patients without HLA-A2 expression, 18/38 (47%), although the difference was not statistically significant (P = 0.17). Neither was there a significant association between HLA-A2/MAGE-3 co-expression and survival (P = 0.15, logrank test). We conclude that there is no dear evidence for elimination of lung cancers co-expressing HLA-A? and MAGE-3 in vivo. Approximately 10% (5/55) of Japanese lung cancer patients are potential candidates for MAGE-3-based immunotherapy. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.