Distribution of HLA class I altered phenotypes in colorectal carcinomas:: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21
Distribution of HLA class I altered phenotypes in colorectal carcinomas:: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21
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DOI：
10.1007/s00251-004-0692-z
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发表时间：
2004-07-01
期刊：
影响因子：
3.2
通讯作者：
Garrido, F
中科院分区：
文献类型：
--
作者：
Maleno, I;Cabrera, CM;Garrido, F
HLA I类缺失或下调是肿瘤细胞用于避免细胞毒性T淋巴细胞识别肿瘤的广泛机制，从而有利于肿瘤免疫逃逸。多种机制负责这些HLA I类改变。在不同的上皮性肿瘤中，6-50%的病例发生染色体区域6p21.3的杂合性缺失（洛），导致HLA单倍型缺失，这取决于肿瘤实体。在本文中，我们报告的洛频率在6p 21在95结直肠癌（CRC）先前分析改变HLA I类表达与免疫组织化学技术。我们使用位于6号染色体上的选定STR标记的PCR微卫星扩增来鉴定来自显微切割的肿瘤组织和周围间质的DNA的洛缺失。在显微切割的基质和肿瘤细胞中进行序列特异性寡核苷酸分析以进行HLA分型，并检测HLA单倍型丢失。CRC中HLA单倍型丢失的频率很高（40%）。8例肿瘤显示微卫星不稳定。我们有时观察到两种或两种以上的机制负责HLA改变同一HLA改变的表型，如洛和HLA I类完全丢失。在25个肿瘤（26%）没有HLA I类改变可以确定。这些数据可能与接受基于T细胞的免疫治疗的CRC患者相关。
HLA class I loss or down-regulation is a widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic T lymphocytes, and thus favor tumor immune escape. Multiple mechanisms are responsible for these HLA class I alterations. In different epithelial tumors, loss of heterozygosity (LOH) at chromosome region 6p21.3, leading to HLA haplotype loss, occurs in 6-50% of all cases depending on the tumor entity. In this paper we report the frequency of LOH at 6p21 in 95 colorectal carcinomas (CRC) previously analyzed for altered HLA class I expression with immunohistological techniques. We used PCR microsatellite amplification of selected STR markers located on Chromosome 6 to identify LOH with DNA from microdissected tumor tissues and the surrounding stroma. Sequence-specific oligonucleotide analysis was performed in microdissected stroma and tumor cells for HLA typing, and to detect HLA haplotype loss. A high frequency (40%) of HLA haplotype loss was found in CRC. Eight tumors showed microsatellite instability. We sometimes observed two or more mechanisms responsible for HLA alteration within the same HLA-altered phenotype, such as LOH and HLA class I total loss. In 25 tumors (26%) no HLA class I alteration could be identified. These data are potentially relevant for CRC patients undergoing T-cell-based immunotherapy.