Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer
Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer
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DOI：
10.1158/0008-5472.can-10-2907
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发表时间：
2011-02-15
期刊：
影响因子：
11.2
通讯作者：
Galon, Jerome
中科院分区：
文献类型：
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作者：
Tosolini, Marie;Kirilovsky, Amos;Galon, Jerome
肿瘤微环境包括免疫T细胞亚群的复杂网络。在这项研究中，我们系统地分析了人类结直肠癌中细胞毒性T细胞和不同辅助T细胞亚群之间的平衡，并将其对无病生存的影响联系起来。对125例结直肠肿瘤冰冻标本进行免疫相关基因分析。浸润的细胞毒性T细胞、Treg、Th 1和Th 17细胞也在肿瘤的中心和浸润边缘定量。通过相关矩阵的分层聚类，我们鉴定了与Th 17（RORC，IL 17 A），Th 2（IL 4，IL 5，IL 13），Th 1（Tbet，IRF 1，IL 12 Rb 2，STAT 4）和细胞毒性（GNLY，GZMB，PRF 1）相关的基因的功能簇。Th 17簇高表达的患者预后差，而Th 1簇高表达的患者无病生存期延长。相比之下，没有一个Th 2簇是预后的预测。细胞毒性/Th 1和Th 17簇的组合分析提高了区分复发的能力。肿瘤组织中IL 17+细胞和CD 8+细胞密度的原位分析证实了该结果。我们的研究结果表明，功能性Th 1和Th 17簇对结直肠癌患者的生存率产生相反的影响，它们提供了可能改善预后的补充信息。Cancer Res; 71（4）; 1263-71.（C）2011年《非洲标准化评论》。
The tumor microenvironment includes a complex network of immune T-cell subpopulations. In this study, we systematically analyzed the balance between cytotoxic T cells and different subsets of helper T cells in human colorectal cancers and we correlated their impact on disease-free survival. A panel of immune related genes were analyzed in 125 frozen colorectal tumor specimens. Infiltrating cytotoxic T cells, Treg, Th1, and Th17 cells were also quantified in the center and the invasive margin of the tumors. By hierarchical clustering of a correlation matrix we identified functional clusters of genes associated with Th17 (RORC, IL17A), Th2 (IL4, IL5, IL13), Th1 (Tbet, IRF1, IL12Rb2, STAT4), and cytotoxicity (GNLY, GZMB, PRF1). Patients with high expression of the Th17 cluster had a poor prognosis, whereas patients with high expression of the Th1 cluster had prolonged disease-free survival. In contrast, none of the Th2 clusters were predictive of prognosis. Combined analysis of cytotoxic/Th1 and Th17 clusters improved the ability to discriminate relapse. In situ analysis of the density of IL17+ cells and CD8+ cells in tumor tissues confirmed the results. Our findings argue that functional Th1 and Th17 clusters yield opposite effects on patient survival in colorectal cancer, and they provide complementary information that may improve prognosis. Cancer Res; 71(4); 1263-71. (C)2011 AACR.