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Pan-cancer deconvolution of tumour composition using DNA methylation

Chakravarthy, Ankur, Furness, Andrew, Joshi, Kroopa, Ghorani, Ehsan, Ford, Kirsty, Ward, Matthew J., King, Emma V., Lechner, Matt, Marafioti, Teresa, Quezada, Sergio A., and others. (2018) Pan-cancer deconvolution of tumour composition using DNA methylation. Nature Communications, 9 (1). ISSN 2041-1723. (doi:10.1038/s41467-018-05570-1) (KAR id:68522)

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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.

Item Type: Article
DOI/Identification number: 10.1038/s41467-018-05570-1
Uncontrolled keywords: Cancer genomics, Cancer microenvironment, Epigenomics, Predictive medicine
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Tim Fenton
Date Deposited: 09 Aug 2018 07:27 UTC
Last Modified: 29 May 2019 20:58 UTC
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