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Sensitive and frequent identification of high avidity neo-epitope specific CD8 + T cells in immunotherapy-naive ovarian cancer

Author

Listed:
  • Sara Bobisse

    (University of Lausanne)

  • Raphael Genolet

    (University of Lausanne)

  • Annalisa Roberti

    (University of Pennsylvania)

  • Janos L. Tanyi

    (University of Pennsylvania)

  • Julien Racle

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • Brian J. Stevenson

    (Swiss Institute of Bioinformatics)

  • Christian Iseli

    (Swiss Institute of Bioinformatics)

  • Alexandra Michel

    (University of Lausanne)

  • Marie-Aude Bitoux

    (University of Lausanne)

  • Philippe Guillaume

    (University of Lausanne)

  • Julien Schmidt

    (University of Lausanne)

  • Valentina Bianchi

    (University of Lausanne)

  • Denarda Dangaj

    (University of Lausanne)

  • Craig Fenwick

    (Lausanne University Hospital)

  • Laurent Derré

    (Lausanne University Hospital)

  • Ioannis Xenarios

    (Swiss Institute of Bioinformatics)

  • Olivier Michielin

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • Pedro Romero

    (University of Lausanne)

  • Dimitri S. Monos

    (The Children’s Hospital of Philadelphia)

  • Vincent Zoete

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • David Gfeller

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • Lana E. Kandalaft

    (University of Lausanne
    University of Pennsylvania)

  • George Coukos

    (University of Lausanne)

  • Alexandre Harari

    (University of Lausanne)

Abstract

Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8+ T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition is discordant between circulating T cells and TILs, and is more likely to be found among TILs, which display higher functional avidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8+ T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors.

Suggested Citation

  • Sara Bobisse & Raphael Genolet & Annalisa Roberti & Janos L. Tanyi & Julien Racle & Brian J. Stevenson & Christian Iseli & Alexandra Michel & Marie-Aude Bitoux & Philippe Guillaume & Julien Schmidt & , 2018. "Sensitive and frequent identification of high avidity neo-epitope specific CD8 + T cells in immunotherapy-naive ovarian cancer," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03301-0
    DOI: 10.1038/s41467-018-03301-0
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