LOH at 6p21.3 region and HLA class I altered phenotypes in bladder carcinomas
LOH at 6p21.3 region and HLA class I altered phenotypes in bladder carcinomas
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DOI：
10.1007/s00251-006-0111-8
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发表时间：
2006-07-01
期刊：
影响因子：
3.2
通讯作者：
Garrido, Federico
中科院分区：
文献类型：
--
作者：
Maleno, Isabel;Romero, Jose Maria;Garrido, Federico
HLA I 类抗原表达的变化在不同的上皮肿瘤中经常被描述，并且被认为有利于肿瘤免疫逃避 T 淋巴细胞识别。多种分子机制导致这些 HLA I 类肿瘤表型的改变。有些是结构缺陷，导致对干扰素治疗无反应。其他包括调节机制的改变，可以通过用不同的细胞因子治疗肿瘤细胞来开启。属于第一组的一个重要机制是染色体区域 6p21.3 的杂合性丢失 (LOH)。这可能导致 HLA 单倍型丢失。在这项研究中，研究了 69 例膀胱癌中 6p21 染色体区域的 LOH 频率。短串联重复分析表明，35% 的病例在该染色体区域存在 LOH。通过考虑这些结果以及我们小组先前发表的免疫组织学发现，我们确定了膀胱癌中 HLA I 类改变表型的分布模式。膀胱癌中最常见的表型改变是HLA I类表达完全缺失（17例，25%），其次是与HLA单倍型缺失相关的表型11（12例，17.5%）和HLA等位基因缺失（10例，14.5%）。 9 例 (13%) 被归类为具有复合表型，5 例 (7%) 被归类为 HLA 基因座丢失，16 例 (23%) 未检测到 HLA 表达变化。该报告的一个重要结论是，需要结合不同的分子和免疫组织学技术来精确定义哪些 HLA 等位基因在肿瘤进展过程中丢失，并描述这些丢失的潜在机制。当癌症患者被纳入旨在刺激不同免疫效应机制的免疫治疗方案时，应该进行这些研究。
Alterations in HLA class I antigen expression have been frequently described in different epithelial tumors and are thought to favor tumor immune escape from T lymphocyte recognition. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes. Some are structural defects that produce unresponsiveness to treatment with interferons. Others include alterations in regulatory mechanisms that can be switched on by treatment of tumor cells with different cytokines. One important mechanism belonging to the first group is loss of heterozygosity (LOH) at chromosome region 6p21.3,. which can lead to HLA haplotype loss. In this investigation, the frequency of LOH at 6p21 chromosome region was studied in 69 bladder carcinomas. Short tandem repeat analysis showed that 35% of cases had LOH in this chromosome region. By considering these results together with immunohistological findings previously published by our group, we identified a distribution pattern of HLA class I altered phenotypes in bladder cancer. The most frequently altered phenotype in bladder carcinomas was total loss of HLA class I expression (17 cases, 25%), followed by phenotype 11 associated with HLA haplotype loss (12 cases, 17.5%), and HLA allelic loss (ten cases, 14.5%). Nine cases (13%) were classified as having a compound phenotype, five cases (7%) as having HLA locus loss, and in 16 cases (23%) no alteration in HLA expression was detected. An important conclusion of this report is that a combination of different molecular and immunohistological techniques is required to precisely define which HLA alleles are lost during tumor progression and to characterize the underlying mechanisms of these losses. These studies should be performed when a cancer patient is to be included in an immunotherapy protocol that aims to stimulate different immune effector mechanisms.