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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_10AE95ADCEE8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sensitive and frequent identification of high avidity neo-epitope specific CD8 + T cells in immunotherapy-naive ovarian cancer.
Journal
Nature communications
Author(s)
Bobisse S., Genolet R., Roberti A., Tanyi J.L., Racle J., Stevenson B.J., Iseli C., Michel A., Le Bitoux M.A., Guillaume P., Schmidt J., Bianchi V., Dangaj D., Fenwick C., Derré L., Xenarios I., Michielin O., Romero P., Monos D.S., Zoete V., Gfeller D., Kandalaft L.E., Coukos G., Harari A.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
15/03/2018
Peer-reviewed
Oui
Volume
9
Number
1
Pages
1092
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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 <sup>+</sup> 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 <sup>+</sup> 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.

Keywords
Antigens, Neoplasm/immunology, CD8-Positive T-Lymphocytes/metabolism, Epitopes, T-Lymphocyte/immunology, Epitopes, T-Lymphocyte/metabolism, Female, Humans, Immunotherapy/methods, Lymphocytes, Tumor-Infiltrating/metabolism, Ovarian Neoplasms/immunology, Ovarian Neoplasms/metabolism, Ovarian Neoplasms/therapy, Receptors, Antigen, T-Cell/genetics
Pubmed
Web of science
Open Access
Yes
Create date
22/03/2018 20:23
Last modification date
20/08/2019 13:37
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