%0 Generic %A Chakravarthy, A %A Furness, A %A Joshi, K %A Ghorani, E %A Ford, K %A Ward, M %A King, E %A Lechner, M %A Marafioti, T %A Quezada, S %A Thomas, G %A Feber, A %A Fenton, T %C Cold Spring Harbor, NY, USA %D 2018 %F discovery:10091068 %I BioRxiv %T Pan-cancer deconvolution of cellular composition identifies molecular correlates of antitumour immunity and checkpoint blockade response %U https://discovery.ucl.ac.uk/id/eprint/10091068/ %X The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a novel 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 hot tumours, 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 and define a catalogue of novel and known mediators of active antitumour immunity, deriving biomarkers and potential targets for precision immunotherapy. %Z The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license (http://creativecommons.org/licenses/by/4.0/).