胚系基因对肿瘤免疫景观的贡献。
Germline genetic contribution to the immune landscape of cancer.
机构信息
Department of Population Sciences, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Biological Sciences and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar; Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon.
出版信息
Immunity. 2021 Feb 9;54(2):367-386.e8. doi: 10.1016/j.immuni.2021.01.011.
Understanding the contribution of the host's genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling. Common variants of IFIH1, TMEM173 (STING1), and TMEM108 were associated with differential interferon signaling and variants mapping to RBL1 correlated with T cell subset abundance. Pathogenic or likely pathogenic variants in BRCA1 and in genes involved in telomere stabilization and Wnt-β-catenin also acted as immune modulators. Our findings provide evidence for the impact of germline genetics on the composition and functional orientation of the tumor immune microenvironment. The curated datasets, variants, and genes identified provide a resource toward further understanding of tumor-immune interactions.
了解宿主遗传背景对癌症免疫的贡献可能会导致免疫疗法的分层改善，并确定新的治疗靶点。我们研究了常见和罕见种系变异对 TCGA 中约 9000 名癌症患者的 139 种明确免疫特征的影响。在 NK 细胞和 T 细胞亚群浸润以及干扰素信号方面观察到高遗传力。IFIH1、TMEM173（STING1）和 TMEM108 的常见变异与不同的干扰素信号相关，而映射到 RBL1 的变异与 T 细胞亚群丰度相关。BRCA1 中的致病性或可能致病性变异以及涉及端粒稳定和 Wnt-β-连环蛋白的基因中的变异也作为免疫调节剂发挥作用。我们的研究结果为种系遗传学对肿瘤免疫微环境的组成和功能定向的影响提供了证据。经过精心整理的数据集、变异和基因为进一步了解肿瘤免疫相互作用提供了资源。
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