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.

Details

Title
Sensitive and frequent identification of high avidity neo-epitope specific CD8 + T cells in immunotherapy-naive ovarian cancer
Author
Bobisse, Sara 1 ; Genolet, Raphael 1 ; Roberti, Annalisa 2 ; Tanyi, Janos L 2 ; Racle, Julien 3   VIAFID ORCID Logo  ; Stevenson, Brian J 4 ; Iseli, Christian 4 ; Michel, Alexandra 1 ; Marie-Aude Le Bitoux 1 ; Guillaume, Philippe 1 ; Schmidt, Julien 1 ; Bianchi, Valentina 1 ; Dangaj, Denarda 1 ; Fenwick, Craig 5 ; Derré, Laurent 6   VIAFID ORCID Logo  ; Xenarios, Ioannis 4 ; Michielin, Olivier 3 ; Romero, Pedro 1 ; Monos, Dimitri S 7 ; Zoete, Vincent 3 ; Gfeller, David 3 ; Kandalaft, Lana E 8 ; Coukos, George 1 ; Harari, Alexandre 1   VIAFID ORCID Logo 

1  Department of Oncology, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland 
2  Ovarian Cancer Research Center, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 
3  Department of Oncology, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland 
4  Swiss Institute of Bioinformatics, Lausanne, Switzerland 
5  Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital, Lausanne, Switzerland 
6  Urology Research Unit, Lausanne University Hospital, Lausanne, Switzerland 
7  Department of Pathology and Laboratory Medicine, Immunogenetics Laboratory, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA 
8  Department of Oncology, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland; Ovarian Cancer Research Center, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 
Pages
1-10
Publication year
2018
Publication date
Mar 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-03301-0
ProQuest document ID
2014349088
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.