ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer.
ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer.
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DOI：
10.1016/j.ebiom.2018.08.003
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发表时间：
2018-09
期刊：
影响因子：
11.1
通讯作者：
Cai SJ
中科院分区：
文献类型：
--
作者：
Hu X;Li YQ;Li QG;Ma YL;Peng JJ;Cai SJ
结直肠肿瘤组织中的肿瘤浸润淋巴细胞（tumor-浸润淋巴细胞，TIL）与良好预后显著相关，如CD8+淋巴细胞，也称为肿瘤反应性淋巴细胞。然而，并不是所有的肿瘤浸润性T细胞都对患者有益。因此，鉴定一种生物标志物来区分这些肿瘤反应性淋巴细胞是非常有益的。我们研究了ITGAE是否可以用于区分结直肠癌（CRC）中的反应性CD8+淋巴细胞。本研究使用TCGA结直肠癌数据集（n1 = 492,n2 = 386）和FUSCC数据集（n3 = 276）。进一步研究了ITGAE+细胞的表型和机制基础。在TCGA的训练和测试集中，ITGAE表达与细胞毒性T细胞标志物（CD8/CD3/PD1）密切相关，独立预测更长的无病生存期（DFS）和总生存期（OS）。与此相一致，ITGAE+淋巴细胞与生存率之间的关联已在FUSCC队列中得到证实（P = .026）。与CD8共染色的ITGAE +细胞优先位于肿瘤中。有趣的是，ITGAE+淋巴细胞倾向于与上皮-间质转化（EMT）相关，伴随着Snail表达减少和E-cadherin表达增加。最后，基因集富集分析显示，高ITGAE+ TIL组免疫激活显著富集，同时emt相关通路富集。由于肿瘤反应性CD8+ t细胞的特异性表达，ITGAE可能是快速识别CRC中免疫浸润的有希望的生物标志物。ITGAE表达独立预测结直肠癌患者更长的无病生存期（DFS）和总生存期（OS）。我们首次在结直肠癌中证明ITGAE+ CD8+淋巴细胞浸润在抗肿瘤免疫应答中起着至关重要的作用，ITGAE已被确定为肿瘤反应性CD8+ TIL的生物标志物。在机制上，ITGAE+淋巴细胞甚至可能与干扰素反应趋化因子和EMT信号相关联，从而作为结直肠癌的独立预测因子。
Tumor-infiltrating lymphocytes (TIL) in colorectal tumor tissue are significantly correlated with a favorable prognosis, such as CD8+ lymphocytes, which are also called tumor-reactive lymphocytes. However, not all tumor-infiltrating T cells confer benefit to patients. Therefore, it is of substantial benefit to identify a biomarker to demarcate these tumor-reactive lymphocytes. We investigated whether ITGAE could be used to discriminate reactive CD8+ lymphocytes in colorectal cancer (CRC). TCGA colorectal cancer data sets (n1 = 492, n2 = 386) and FUSCC set (n3 = 276) were used in this study. Further phenotyping of ITGAE+ cells and the mechanistic basis were investigated. In the training and testing sets from TCGA, ITGAE expression, which is strongly correlated with cytotoxic T cell markers (CD8/CD3/PD1), independently predicted longer disease-free survival (DFS) and overall survival (OS). In line with this, the association between ITGAE+ lymphocytes and survival has been confirmed in the FUSCC cohort for validation (P = .026). ITGAE + cells in the series always co-stained with CD8 were preferentially located in the tumor. Interestingly, ITGAE+ lymphocytes tended to associate with the epithelial–mesenchymal transition (EMT) with decreased Snail and increased E-cadherin expression accompanied. Finally, gene set enrichment analysis showed that immune activation was significantly enriched in the high ITGAE+ TIL group, accompanied by enriched EMT-related pathways. Because of the specified expression of tumor-reactive CD8+ T-cells, ITGAE may be a promising biomarker for the rapid identification of immune infiltration in CRC. ITGAE expression independently predicted longer disease-free survival (DFS) and overall survival (OS) in colorectal cancers. ITGAE could be used to discriminate CD8+ TIL populations We demonstrate here in colorectal cancers for the first time that ITGAE+ CD8+ lymphocytes infiltration plays a vital role in the antitumor immune response and ITGAE has been identified as a biomarker of tumor-reactive CD8+ TIL. In mechanism, ITGAE+ lymphocytes may even associate with interferon-response chemokines and EMT signaling, then serves as an independent predictor in colorectal cancers.
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DOI：
10.1084/jem.20061524
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
13
作者：
Neville, Lewis F.;Mathiak, Guenther;Bagasra, Omar
通讯作者：
Bagasra, Omar
影响因子：
4.4
作者：
Djenidi, Faycal;Adam, Julien;Mami-Chouaib, Fathia
通讯作者：
Mami-Chouaib, Fathia
影响因子：
254.7
作者：
Siegel, Rebecca L.;Miller, Kimberly D.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
11.2
作者：
Franciszkiewicz, Katarzyna;Le Floc'h, Audrey;Mami-Chouaib, Fathia
通讯作者：
Mami-Chouaib, Fathia