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Pan-cancer deconvolution of tumour composition using DNA methylation

Author

Listed:
  • Ankur Chakravarthy

    (University College London
    Princess Margaret Cancer Centre)

  • 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)

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.

Suggested Citation

  • 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 Febe, 2018. "Pan-cancer deconvolution of tumour composition using DNA methylation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05570-1
    DOI: 10.1038/s41467-018-05570-1
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    Cited by:

    1. Marjan M. Naeini & Felicity Newell & Lauren G. Aoude & Vanessa F. Bonazzi & Kalpana Patel & Guy Lampe & Lambros T. Koufariotis & Vanessa Lakis & Venkateswar Addala & Olga Kondrashova & Rebecca L. John, 2023. "Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Andrew J. Murphy & Changde Cheng & Justin Williams & Timothy I. Shaw & Emilia M. Pinto & Karissa Dieseldorff-Jones & Jack Brzezinski & Lindsay A. Renfro & Brett Tornwall & Vicki Huff & Andrew L. Hong , 2023. "Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Grayson A. Herrgott & James M. Snyder & Ruicong She & Tathiane M. Malta & Thais S. Sabedot & Ian Y. Lee & Jacob Pawloski & Guilherme G. Podolsky-Gondim & Karam P. Asmaro & Jiaqi Zhang & Cara E. Cannel, 2023. "Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Theodore Sakellaropoulos & Catherine Do & Guimei Jiang & Giulia Cova & Peter Meyn & Dacia Dimartino & Sitharam Ramaswami & Adriana Heguy & Aristotelis Tsirigos & Jane A. Skok, 2024. "MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Ankur Chakravarthy & Ian Reddin & Stephen Henderson & Cindy Dong & Nerissa Kirkwood & Maxmilan Jeyakumar & Daniela Rothschild Rodriguez & Natalia Gonzalez Martinez & Jacqueline McDermott & Xiaoping Su, 2022. "Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Caroline Hoffmann & Floriane Noel & Maximilien Grandclaudon & Lucile Massenet-Regad & Paula Michea & Philemon Sirven & Lilith Faucheux & Aurore Surun & Olivier Lantz & Mylene Bohec & Jian Ye & Weihua , 2022. "PD-L1 and ICOSL discriminate human Secretory and Helper dendritic cells in cancer, allergy and autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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