Varn Frederick S, Andrews Erik H, Mullins David W, Cheng Chao
Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03766, USA.
Nat Commun. 2016 Jan 4;7:10248. doi: 10.1038/ncomms10248.
Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these results allow for a detailed and personalized assessment of the patient immune response to a tumour. When combined with routinely collected patient biopsy genomic data, this method can enable a richer understanding of the complex interplay between the host immune system and cancer.
造血细胞中活跃的转录程序能够实现多种功能,包括去分化、先天免疫和适应性免疫。了解这些程序在癌症背景下如何发挥作用,可以为宿主免疫反应、癌症严重程度和潜在治疗反应提供有价值的见解。在这里,我们提出了一种方法,该方法使用200多种小鼠造血细胞的转录组来推断人类乳腺肿瘤中存在的谱系特异性造血活性。将这种活性与患者生存率和肿瘤纯度相关联,结果显示许多细胞类型的转录程序会影响患者预后,并且在高淋巴细胞浸润的环境中存在。总体而言,这些结果有助于对患者对肿瘤的免疫反应进行详细且个性化的评估。当与常规收集的患者活检基因组数据相结合时,这种方法能够更深入地理解宿主免疫系统与癌症之间的复杂相互作用。