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

• Published in: Nature communications Vol. 9; no. 1; pp. 1092 - 10
• Main Authors: Bobisse, Sara, Genolet, Raphael, Roberti, Annalisa, Tanyi, Janos L., Racle, Julien, Stevenson, Brian J., Iseli, Christian, Michel, Alexandra, Le Bitoux, Marie-Aude, Guillaume, Philippe, Schmidt, Julien, Bianchi, Valentina, Dangaj, Denarda, Fenwick, Craig, Derré, Laurent, Xenarios, Ioannis, Michielin, Olivier, Romero, Pedro, Monos, Dimitri S., Zoete, Vincent, Gfeller, David, Kandalaft, Lana E., Coukos, George, Harari, Alexandre
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.03.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 38/91; 45/23; 631/67/1059/2325; 631/67/1517/1709; 631/67/580; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - immunology; Avidity; Cancer; Cancer immunotherapy; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; Epitopes; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Female; Humanities and Social Sciences; Humans; Immunotherapy; Immunotherapy - methods; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - metabolism; multidisciplinary; Mutation; Ovarian cancer; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - therapy; Receptors, Antigen, T-Cell - genetics; Science; Science (multidisciplinary); Tumor-infiltrating lymphocytes; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03301-0

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. Epithelial ovarian cancer (EOC) has low mutational load. Here the authors analyze circulating and tumor-infiltrating lymphocytes (TILs) from 19 EOC patients and report frequent recovery of neo-antigen-reactive T cells from both compartments but with distinct TCR repertoires that have higher affinity in TILs.