Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome
Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome
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DOI：
10.1172/jci127046
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发表时间：
2019-10-01
影响因子：
15.9
通讯作者：
Lee, Peter P.
中科院分区：
文献类型：
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作者：
Fakih, Marwan;Ouyang, Ching;Lee, Peter P.
肿瘤微环境(TME)中免疫细胞浸润的预后价值已通过组织学和基因组学方法广泛研究。基于T细胞浸润的积极预后价值，免疫球蛋白已被开发并验证用于预测结直肠癌(CRC)的复发风险。此外，在多种癌症类型中观察到共识T辅助细胞1(Th-1)免疫反应和良好的临床结果之间的关联。在这里，我们重新分析了来自癌症基因组图谱(TCGA)和NCBI基因表达总览(NCBI-GEO)的公共基因组数据集，并对一组结直肠肿瘤进行了多光谱免疫组织化学(IHC)。我们确定并描述了一组风险人群，约占10%的CRC患者，肿瘤内CD8(+)T细胞高度浸润，但预后较差。这些肿瘤包括微卫星不稳定(MSI)和稳定(MSS)两种表型，并具有高密度的肿瘤相关巨噬细胞(TAM)，表达CD274(程序性死亡配体1[PD-L1])，转化生长因子-β激活，以及以免疫反应和检查点基因过度表达为特征的免疫过度驱动特征。我们的研究结果表明，尽管CD8(+)T细胞浸润较高，但结直肠癌患者的预后可能较差，并提供了CD274作为一种简单的生物标志物来识别这些患者。
The prognostic value of immune cell infiltration within the tumor microenvironment (TME) has been extensively investigated via histological and genomic approaches. Based on the positive prognostic value of T cell infiltration, Immunoscore has been developed and validated for predicting risk of recurrence for colorectal cancer (CRC). Also, association between a consensus T helper 1 (Th-1) immune response and favorable clinical outcomes has been observed across multiple cancer types. Here, we reanalyzed public genomic data sets from The Cancer Genome Atlas (TCGA) and NCBI Gene Expression Omnibus (NCBI-GEO) and performed multispectral immunohistochemistry (IHC) on a cohort of colorectal tumors. We identified and characterized a risk group, representing approximately 10% of CRC patients, with high intratumoral CD8(+) T cell infiltration, but poor prognosis. These tumors included both microsatellite instable (MSI) and stable (MSS) phenotypes and had a high density of tumor-associated macrophages (TAMs) that expressed CD274 (programmed death-ligand 1 [PD-L1]), TGF-beta activation, and an immune overdrive signature characterized by the overexpression of immune response and checkpoint genes. Our findings illustrate that CRC patients may have poor prognosis despite high CD8(+) T cell infiltration and provide CD274 as a simple biomarker for identifying these patients.