dc.contributor.author | Chakravarthy, A | |
dc.contributor.author | Furness, A | |
dc.contributor.author | Joshi, K | |
dc.contributor.author | Ghorani, E | |
dc.contributor.author | Ford, K | |
dc.contributor.author | Ward, MJ | |
dc.contributor.author | King, EV | |
dc.contributor.author | Lechner, M | |
dc.contributor.author | Marafioti, T | |
dc.contributor.author | Quezada, SA | |
dc.contributor.author | Thomas, GJ | |
dc.contributor.author | Feber, A | |
dc.contributor.author | Fenton, TR | |
dc.date.accessioned | 2020-08-25T15:41:34Z | |
dc.date.issued | 2018-08-13 | |
dc.identifier.citation | Nature communications, 2018, 9 (1), pp. 3220 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4005 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-018-05570-1 | |
dc.description.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. | |
dc.format | Electronic | |
dc.format.extent | 3220 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Th1 Cells | |
dc.subject | Cell Line, Tumor | |
dc.subject | Macrophages | |
dc.subject | Humans | |
dc.subject | Papillomaviridae | |
dc.subject | Proteome | |
dc.subject | Reproducibility of Results | |
dc.subject | Cell Cycle | |
dc.subject | DNA Methylation | |
dc.subject | Mutation | |
dc.subject | Genome, Human | |
dc.subject | Transcriptome | |
dc.subject | Squamous Cell Carcinoma of Head and Neck | |
dc.title | Pan-cancer deconvolution of tumour composition using DNA methylation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-07-10 | |
rioxxterms.versionofrecord | 10.1038/s41467-018-05570-1 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-08-13 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 9 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Furness, Andrew | |
dc.contributor.icrauthor | Feber, Andrew | |