Scientific publications

Identification of HLA class I-restricted immunogenic neoantigens in triple negative breast cancer

Nov 2, 2022 | Magazine: Frontiers in Immunology

Belén Aparicio  1   2   3 , David Repáraz  1   2   3 , Marta Ruiz  1   2   3 , Diana Llopiz  1   2   3 , Leyre Silva  1   2   3 , Enric Vercher  1   2   3 , Patrick Theunissen  1   2   3 , Ibon Tamayo  1   3 , Cristian Smerdou  1   3 , Ana Igea  1   3 , Marta Santisteban  3   4 , Cristina Gónzalez-Deza  4 , Juan J Lasarte  1   3 , Sandra Hervás-Stubbs  1   2   3 , Pablo Sarobe  1   2   3


Immune checkpoint inhibitor (ICI)-based immunotherapy in triple negative breast cancer (TNBC) is achieving limited therapeutic results, requiring the development of more potent strategies.

Combination of ICI with vaccination strategies would enhance antitumor immunity and response rates to ICI in patients having poorly infiltrated tumors. In heavily mutated tumors, neoantigens (neoAgs) resulting from tumor mutations have induced potent responses when used as vaccines.

Thus, our aim was the identification of immunogenic neoAgs suitable as vaccines in TNBC patients. By using whole exome sequencing, RNAseq and HLA binding algorithms of tumor samples from a cohort of eight TNBC patients, we identified a median of 60 mutations/patient, which originated a putative median number of 98 HLA class I-restricted neoAgs.

Considering a group of 27 predicted neoAgs presented by HLA-A*02:01 allele in two patients, peptide binding to HLA was experimentally confirmed in 63% of them, whereas 55% were immunogenic in vivo in HLA-A*02:01+ transgenic mice, inducing T-cells against the mutated but not the wild-type peptide sequence. Vaccination with peptide pools or DNA plasmids expressing these neoAgs induced polyepitopic T-cell responses, which recognized neoAg-expressing tumor cells.

These results suggest that TNBC tumors harbor neoAgs potentially useful in therapeutic vaccines, opening the way for new combined immunotherapies.

CITATION  Front Immunol. 2022 Nov 2;13:985886.  doi: 10.3389/fimmu.2022.985886.  eCollection 2022

Our authors

Belén Aparicio de la Torre
David Repáraz Pernaut
Dr. Marta Ruiz Egozcue
Research Technician Peptide Research Group
Dr. Diana Llópiz Khatchikian
Leyre Silva Vergara
Investigador predoctoral del Programa de Inmunología e Inmunoterapia del Cima Universidad de Navarra
Enric Vercher Herráez
Ibon Tamayo Uría
Research Collaborator Bioinformatics Platform
Dr. Sandra Hervás Stubbs
Researcher | Principal Investigator Adoptive Cell Therapy Research Group