Chakravarthy, A;
Furness, A;
Joshi, K;
Ghorani, E;
Ford, K;
Ward, MJ;
King, EV;
... Fenton, TR; + view all
(2018)
Pan-cancer deconvolution of tumour composition using DNA methylation.
Nature Communications
, 9
, Article 3220. 10.1038/s41467-018-05570-1.
Preview |
Text (Published article)
s41467-018-05570-1.pdf - Published Version Download (4MB) | Preview |
![[thumbnail of Supplementary files]](https://discovery.ucl.ac.uk/style/images/fileicons/archive.png) |
Archive (Supplementary files)
Chakravarthy_s41467-018-05570-1_suppl.zip Download (15MB) |
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.
| Type: | Article |
|---|---|
| Title: | Pan-cancer deconvolution of tumour composition using DNA methylation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-018-05570-1 |
| Publisher version: | https://doi.org/10.1038/s41467-018-05570-1 |
| Language: | English |
| Additional information: | © The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10055128 |
Archive Staff Only
 |
View Item |
