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

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, Valentina Bianchi, Denarda Dangaj, Craig Fenwick, Laurent Derré, Ioannis Xenarios, Olivier Michielin, Pedro Romero, Dimitri S. Monos, Vincent Zoete, David Gfeller, Lana E. Kandalaft, George Coukos () and Alexandre Harari ()
Additional contact information
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
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
Pedro Romero: University of Lausanne
Dimitri S. Monos: The Children’s Hospital of Philadelphia
Vincent Zoete: University of Lausanne
David Gfeller: University of Lausanne
Lana E. Kandalaft: University of Lausanne
George Coukos: University of Lausanne
Alexandre Harari: University of Lausanne

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03301-0

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DOI: 10.1038/s41467-018-03301-0

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