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). Article Number 3220. ISSN 2041-1723. (doi:10.1038/s41467-018-05570-1) (KAR id:68522)
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Official URL: https://doi.org/10.1038/s41467-018-05570-1 |
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.
Item Type: | Article |
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DOI/Identification number: | 10.1038/s41467-018-05570-1 |
Uncontrolled keywords: | Cancer genomics, Cancer microenvironment, Epigenomics, Predictive medicine |
Subjects: | Q Science |
Divisions: | Divisions > Division of Natural Sciences > Biosciences |
Depositing User: | Tim Fenton |
Date Deposited: | 09 Aug 2018 07:27 UTC |
Last Modified: | 05 Nov 2024 12:30 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/68522 (The current URI for this page, for reference purposes) |
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