Pan-cancer deconvolution of tumour composition using DNA methylation.
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Embargo End Date
ICR Authors
Authors
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
Furness, A
Joshi, K
Ghorani, E
Ford, K
Ward, MJ
King, EV
Lechner, M
Marafioti, T
Quezada, SA
Thomas, GJ
Feber, A
Fenton, TR
Document Type
Journal Article
Date
2018-08-13
Date Accepted
2018-07-10
Abstract
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.
Citation
Nature communications, 2018, 9 (1), pp. 3220 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723