Pan-cancer deconvolution of cellular composition identifies molecular correlates of antitumour immunity and checkpoint blockade response

Abstract

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.

ILnc: Prioritizing Long Non-coding RNAs for Pan-cancer Analysis of Immune Cell Infiltration

“…There are also many other algorithms for predicting the level of tumor infiltrating lymphocyte (TIL) in tumor tissue, such as MCP-Counter [19] and EPIC [20]. DNA methylation was also introduced to predict immune cell infiltration [21]. In addition, other deconvolution methods were developed to infer proportions of cell types from bulk transcriptomic data.…”