Institute for Systems Biology, 401 Terry Ave N, Seattle, WA 98109, USA.
Institute for Systems Biology, 401 Terry Ave N, Seattle, WA 98109, USA.
Immunity. 2018 Apr 17;48(4):812-830.e14. doi: 10.1016/j.immuni.2018.03.023. Epub 2018 Apr 5.
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.
我们利用 TCGA 汇编的数据,对超过 10000 个包含 33 种不同癌症类型的肿瘤进行了广泛的免疫基因组分析。在癌症类型之间,我们确定了六个免疫亚型——创伤愈合型、IFN-γ 优势型、炎症型、淋巴细胞耗竭型、免疫安静型和 TGF-β 优势型——其特征是巨噬细胞或淋巴细胞特征、Th1:Th2 细胞比例、肿瘤内异质性程度、非整倍体、新抗原负荷程度、整体细胞增殖、免疫调节基因表达和预后的不同。特定的驱动突变与所有癌症中的白细胞水平降低(CTNNB1、NRAS 或 IDH1)或升高(BRAF、TP53 或 CASP8)相关。细胞内和细胞外网络(转录、microRNAs、拷贝数和表观遗传过程)的多种控制方式参与了肿瘤-免疫细胞的相互作用,无论是在免疫亚型之间还是在其中。我们用于描述这些异质性肿瘤的免疫基因组学管道以及由此产生的数据旨在作为未来靶向研究的资源,以进一步推动该领域的发展。