Pan-cancer deconvolution of tumour composition using DNA methylation.
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Date
2018-08-13Author
Chakravarthy, A
Furness, A
Joshi, K
Ghorani, E
Ford, K
Ward, MJ
King, EV
Lechner, M
Marafioti, T
Quezada, SA
Thomas, GJ
Feber, A
Fenton, TR
Type
Journal Article
Metadata
Show full item recordAbstract
The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: 'immune hot' and 'immune cold', which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity and oncogenic driver events. We demonstrate the existence of such tumour subgroups pan-cancer, link clonal-neoantigen burden to cytotoxic T-lymphocyte infiltration, and show that transcriptional signatures of hot tumours are selectively engaged in immunotherapy responders. We also find that treatment-naive hot tumours are markedly enriched for known immune-resistance genomic alterations, potentially explaining the heterogeneity of immunotherapy response and prognosis seen within this group. Finally, we define a catalogue of mediators of active antitumour immunity, deriving candidate biomarkers and potential targets for precision immunotherapy.
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Subject
Th1 Cells
Cell Line, Tumor
Macrophages
Humans
Papillomaviridae
Proteome
Reproducibility of Results
Cell Cycle
DNA Methylation
Mutation
Genome, Human
Transcriptome
Squamous Cell Carcinoma of Head and Neck
Language
eng
Date accepted
2018-07-10
License start date
2018-08-13
Citation
Nature communications, 2018, 9 (1), pp. 3220 - ?
Publisher
NATURE PUBLISHING GROUP