| Autor: |
Paola Bonaventura, Vincent Alcazer, Virginie Mutez, Laurie Tonon, Juliette Martin, Nicolas Chuvin, Emilie Michel, Rasha E. Boulos, Yann Estornes, Jenny Valladeau-Guilemond, Alain Viari, Qing Wang, Christophe Caux, Stéphane Depil |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Science Advances. 8 |
| ISSN: |
2375-2548 |
| DOI: |
10.1126/sciadv.abj3671 |
| Popis: |
Human endogenous retroviruses (HERVs) represent 8% of the human genome. HERV products may represent tumor antigens relevant for cancer immunotherapy. We developed a bioinformatic approach to identify shared CD8 + T cell epitopes derived from cancer-associated HERVs in solid tumors. Six candidates among the most commonly shared HLA-A2 epitopes with evidence of translation were selected for immunological evaluation. In vitro priming assays confirmed the immunogenicity of these epitopes, which induced high-avidity CD8 + T cell clones. These T cells specifically recognize and kill HLA-A2 + tumor cells presenting HERV epitopes on HLA molecules, as demonstrated by mass spectrometry. Furthermore, epitope-specific CD8 + T cells were identified by dextramer staining among tumor-infiltrating lymphocytes from HLA-A2 + patients with breast cancer. Last, we showed that HERV-specific T cells lyse patient-derived organoids. These shared virus-like epitopes are of major interest for the development of cancer vaccines or T cell–based immunotherapies, especially in tumors with low/intermediate mutational burden. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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