Sensitive and Frequent Identification of High Avidity Neo-epitope Specific CD8 + T-cells in Immunotherapy-naïve Ovarian Cancer

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 allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naïve patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition was discordant between circulating T cells and TILs, and was more likely to be found among TILs, which displayed higher functionalavidity 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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001003916	Cancer exomes consisting of FASTQ paired-end reads from ovary samples	Illumina HiSeq 2500	19
EGAD00001003917	Germline exomes consisting of FASTQ paired-end reads from blood samples	Illumina HiSeq 2500	19
EGAD00001003918	Cancer RNA-seq consisting of FASTQ paired-end reads from ovary samples	Illumina HiSeq 2500	16

Publications	Citations
Sensitive and frequent identification of high avidity neo-epitope specific CD8 <sup>+</sup> T cells in immunotherapy-naive ovarian cancer. Bobisse S, Genolet R, Roberti A, Tanyi JL, Racle J, Stevenson BJ, Iseli C, Michel A, Le Bitoux MA, Guillaume P, Schmidt J, Bianchi V, Dangaj D, Fenwick C, Derré L, Xenarios I, Michielin O, Romero P, Monos DS, Zoete V, Gfeller D, Kandalaft LE, Coukos G, Harari A. Nat Commun 9: 2018 1092	84
Sensitive identification of neoantigens and cognate TCRs in human solid tumors. Arnaud M, Chiffelle J, Genolet R, Navarro Rodrigo B, Perez MAS, Huber F, Magnin M, Nguyen-Ngoc T, Guillaume P, Baumgaertner P, Chong C, Stevenson BJ, Gfeller D, Irving M, Speiser DE, Schmidt J, Zoete V, Kandalaft LE, Bassani-Sternberg M, Bobisse S, Coukos G, Harari A. Nat Biotechnol 40: 2022 656-660	28

Publications

Citations

Sensitive and frequent identification of high avidity neo-epitope specific CD8 <sup>+</sup> T cells in immunotherapy-naive ovarian cancer.
Bobisse S, Genolet R, Roberti A, Tanyi JL, Racle J, Stevenson BJ, Iseli C, Michel A, Le Bitoux MA, Guillaume P, Schmidt J, Bianchi V, Dangaj D, Fenwick C, Derré L, Xenarios I, Michielin O, Romero P, Monos DS, Zoete V, Gfeller D, Kandalaft LE, Coukos G, Harari A. Nat Commun 9: 2018 1092

Sensitive identification of neoantigens and cognate TCRs in human solid tumors.
Arnaud M, Chiffelle J, Genolet R, Navarro Rodrigo B, Perez MAS, Huber F, Magnin M, Nguyen-Ngoc T, Guillaume P, Baumgaertner P, Chong C, Stevenson BJ, Gfeller D, Irving M, Speiser DE, Schmidt J, Zoete V, Kandalaft LE, Bassani-Sternberg M, Bobisse S, Coukos G, Harari A. Nat Biotechnol 40: 2022 656-660