Dataset Information

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

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.

SUBMITTER: Bobisse S

PROVIDER: S-EPMC5854609 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Bobisse Sara S Genolet Raphael R Roberti Annalisa A Tanyi Janos L JL Racle Julien J Stevenson Brian J BJ Iseli Christian C Michel Alexandra A Le Bitoux Marie-Aude MA Guillaume Philippe P Schmidt Julien J Bianchi Valentina V Dangaj Denarda D Fenwick Craig C Derré Laurent L Xenarios Ioannis I Michielin Olivier O Romero Pedro P Monos Dimitri S DS Zoete Vincent V Gfeller David D Kandalaft Lana E LE Coukos George G Harari Alexandre A

Nature communications 20180315 1

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 ...[more]

PMID: 29545564

Similar Datasets

Project description:Background and aimHuman papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools.MethodsInitially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8+ T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8+, nested interferon gamma (IFN-γ)-producing CD4+, and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes.ResultsTwenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from -10.80 to -86.71 kcal/mol. In addition, CD8+ epitope-overlapped segments in CD4+ and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways.ConclusionEven though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8+ and overlapped epitopes provide new insights into HPV vaccine development.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets