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 Le 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, Alexandre Harari, Sara Bobisse, Raphael Genolet, Annalisa Roberti, Janos L Tanyi, Julien Racle, Brian J Stevenson, Christian Iseli, Alexandra Michel, Marie-Aude Le 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, Alexandre Harari
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.
Conflict of interest statement
The authors declare no competing interests.
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References
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