NKG2D ligand expression in human colorectal cancer reveals associations with prognosis and evidence for immunoediting.
NKG2D ligand expression in human colorectal cancer reveals associations with prognosis and evidence for immunoediting.
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DOI：
10.1158/1078-0432.ccr-09-0991
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发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Durrant LG
中科院分区：
文献类型：
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作者：
McGilvray RW;Eagle RA;Watson NF;Al-Attar A;Ball G;Jafferji I;Trowsdale J;Durrant LG
NKG2D与MIC和ULBP/RAET家族的细胞配体结合。这些配体在正常组织中的表达受到限制，但在原发肿瘤中经常表达。NKG2D配体在癌症发生中的作用被认为是重要的，但在如此大的队列中还没有对预后的影响进行调查。在我们的研究中，我们对462例原发大肠肿瘤进行了MIC/ULBP/RAET蛋白表达和NK细胞浸润的筛查。本研究采用肿瘤微阵列技术。NKG2D配体在大多数结直肠肿瘤中都有表达，但表达水平差异很大。MIC(68个月对56个月)或RAET1G(74个月对62个月)的高表达显示患者存活率提高。高水平表达MIC和RAET1G的肿瘤比高水平表达一种配体或低水平表达两种配体的肿瘤显示出77个月的生存期。所有配体的高表达在TNM 1期肿瘤中常见，但在2、3和4期肿瘤中逐渐减少。MIC的表达与NK细胞的浸润有关。这些观察结果与一种免疫编辑机制是一致的，该机制选择失去或减少NKG2D配体表达的肿瘤细胞。MIC和TNM分期相结合是将患者分成8组的最强的生存预测因子，并提示临床评估预后价值。特别令人感兴趣的是MIC低表达的1期患者，他们的存活率与3期患者相似，可能是辅助治疗的候选者。
NKG2D binds to cellular ligands of the MIC and ULBP/RAET family. These ligands have restricted expression in normal tissue, but are frequently expressed on primary tumors. The role of NKG2D ligands is thought to be important in carcinogenesis but prognostic impact has not been investigated in such a large cohort. In our study 462 primary colorectal tumors were screened for expression of all MIC / ULBP / RAET proteins and NK cell infiltration. Tumor microarray technology was used for the purpose of this investigation. NKG2D ligands were expressed by the majority of colorectal tumors; however the level of expression varied considerably. High expression of MIC (68 versus 56 months) or RAET1G (74 versus 62 months) demonstrated improved patient survival. Tumors expressing high levels of MIC and RAET1G showed improved survival of 77 months over tumors that expressed high levels of one ligand or low levels of both. High-level expression of all ligands was frequent in TNM stage 1 tumors, but became progressively less frequent in stage 2, 3 and 4 tumors. Expression of MIC was correlated with NK cellular infiltration. The observations presented are consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced their expression of NKG2D ligands. Combination of MIC and TNM stage was found to be the strongest predictor of survival splitting patients into 8 groups and suggesting prognostic value in clinical assessment. Of particular interest were stage 1 patients with low expression of MIC who had a similar survival to stage 3 patients, and may be candidates for adjuvant therapy.