浸润性 T 细胞毒性和辅助细胞(Th1、Th2、Treg、Th17)在结直肠癌患者中的临床影响。
Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer.
机构信息
INSERM, Integrative Cancer Immunology Team, INSERM U872, Paris, France.
出版信息
Cancer Res. 2011 Feb 15;71(4):1263-71. doi: 10.1158/0008-5472.CAN-10-2907. Epub 2011 Feb 8.
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.
肿瘤微环境包括一个复杂的免疫 T 细胞亚群网络。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 细胞与不同辅助性 T 细胞亚群之间的平衡,并将其与无病生存率相关联。我们分析了 125 个冷冻结直肠肿瘤标本中的一组免疫相关基因。还在肿瘤中心和侵袭边缘量化了浸润性细胞毒性 T 细胞、Treg、Th1 和 Th17 细胞。通过对相关矩阵的层次聚类,我们确定了与 Th17(RORC、IL17A)、Th2(IL4、IL5、IL13)、Th1(Tbet、IRF1、IL12Rb2、STAT4)和细胞毒性(GNLY、GZMB、PRF1)相关的基因功能簇。高表达 Th17 簇的患者预后不良,而高表达 Th1 簇的患者无病生存率延长。相比之下,Th2 簇均与预后无关。细胞毒性/Th1 和 Th17 簇的联合分析提高了区分复发的能力。肿瘤组织中 IL17+细胞和 CD8+细胞密度的原位分析证实了这些结果。我们的研究结果表明,功能性 Th1 和 Th17 簇对结直肠癌患者的生存产生相反的影响,它们提供了互补的信息,可能改善预后。