Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study.
Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study.
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DOI：
10.1186/1471-2407-14-486
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发表时间：
2014-07-05
期刊：
影响因子：
3.8
通讯作者：
Kuppen PJ
中科院分区：
文献类型：
--
作者：
Reimers MS;Engels CC;Putter H;Morreau H;Liefers GJ;van de Velde CJ;Kuppen PJ
逃避免疫监视和抑制免疫系统是肿瘤发生的重要标志。本研究的目的是建立反映直肠肿瘤免疫表型的独特模式，并确定其与患者预后的关系。研究人群包括495例I-IV期未经术前治疗的直肠癌患者，其中组织微阵列（TMA）可用。对该TMA的切片进行化学染色，并定量Foxp 3+细胞（T细胞）的存在以及HLA I类和非经典HLA-E和HLA-G的肿瘤表达。所有标记物，单独和组合，分析临床预后价值。HLA I类抗原的表达（DFS HR 0.637（0.458-0.886），p = 0.013），Foxp 3+浸润高于中位数（OS HR 0.637（0.500-0.813），p < 0.001和DFS HR 0.624）（0.491-0.793），p < 0.001）和HLA-G表达（DFS HR 0.753（0.574-0.989），p = 0.042）与较好的临床预后相关。当这些标志物组合时，具有与不良预后相关的2或3个标志物的患者（HLA I类丧失、Foxp 3+低于中值和弱HLA-G表达）显示出显著更差的存活率（OS和DFS p < 0.001）。这种免疫表型是DFS的独立预测因子（HR 1.56（1.14-2.14），p = 0.019）。总之，直肠肿瘤显示HLA I类表达缺失、Foxp 3+浸润低于中位数和弱HLA-G表达与OS和DFS较差相关。结合这些免疫标记物导致肿瘤免疫表型的产生，其与患者结果相关，并且是直肠癌中重要的独立临床预后标记物。
Evasion of immune surveillance and suppression of the immune system are important hallmarks of tumorigenesis. The goal of this study was to establish distinct patterns that reflect a rectal tumors’ immune-phenotype and to determine their relation to patient outcome. The study population consisted of 495 Stage I-IV non-preoperatively treated rectal cancer patients of which a tissue micro array (TMA) was available. Sections of this TMA were immunohistochemically stained and quantified for presence of Foxp3+ cells (Tregs) and tumor expression of HLA Class I and non-classical HLA-E and HLA-G. All markers were, separate and combined, analyzed for clinical prognostic value. Expression of HLA class I (DFS HR 0.637 (0.458-0.886), p = 0.013), Foxp3+ infiltration above median (OS HR 0.637 (0.500-0.813), p < 0.001 and DFS HR 0.624 (0.491-0.793), p < 0.001) and expression of HLA-G (DFS HR 0.753 (0.574-0.989), p = 0.042) were related to a better clinical prognosis. When these markers were combined, patients with 2 or 3 markers associated with poor prognosis (loss of HLA Class I, Foxp3+ below median, and weak HLA-G expression), showed a significantly worse survival (OS and DFS p < 0.001). This immune-phenotype was an independent predictor for DFS (HR 1.56 (1.14-2.14), p = 0.019). In conclusion, rectal tumors showing loss of HLA class I expression, Foxp3+ infiltration below median and weak HLA-G expression were related to a worse OS and DFS. Combining these immune markers lead to the creation of tumor immune-phenotypes , which related to patient outcome and were significant independent clinical prognostic markers in rectal cancer.
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DOI：
10.1080/110241599750006613
发表时间：
1999-05-01
期刊：
EUROPEAN JOURNAL OF SURGERY
影响因子：
--
作者：
Kapiteijn, E;Kranenbarg, EK;van de Velde, CJH
通讯作者：
van de Velde, CJH
影响因子：
32.4
作者：
Hill, Jonathan A.;Feuerer, Markus;Benoist, Christophe
通讯作者：
Benoist, Christophe
影响因子：
7.3
作者：
Kapiteijn, E;Liefers, GJ;van Krieken, JHJM
通讯作者：
van Krieken, JHJM
影响因子：
3.5
作者：
Li, Jing Nan;Zhao, Li;Qian, Jia Ming
通讯作者：
Qian, Jia Ming
影响因子：
3.8
作者：
Dierssen JW;de Miranda NF;Ferrone S;van Puijenbroek M;Cornelisse CJ;Fleuren GJ;van Wezel T;Morreau H
通讯作者：
Morreau H