Pan-cancer deconvolution of tumour composition using DNA methylation

Ankur Chakravarthy, Andrew Furness, Kroopa Joshi, Ehsan Ghorani, Kirsty Ford, Matthew J. Ward, Emma V. King, Matt Lechner, Teresa Marafioti, Sergio A. Quezada, Gareth J. Thomas, Andrew Feber and Tim R. Fenton ()
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Ankur Chakravarthy: University College London
Andrew Furness: University College London
Kroopa Joshi: University College London
Ehsan Ghorani: University College London
Kirsty Ford: University of Southampton
Matthew J. Ward: University of Southampton
Emma V. King: University of Southampton
Matt Lechner: University College London
Teresa Marafioti: University College London
Sergio A. Quezada: University College London
Gareth J. Thomas: University of Southampton
Andrew Feber: University College London
Tim R. Fenton: University of Kent

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05570-1

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DOI: 10.1038/s41467-018-05570-1

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