Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy

Sci Adv. 2022 Jan 28;8(4):eabj3671. doi: 10.1126/sciadv.abj3671. Epub 2022 Jan 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • CD8-Positive T-Lymphocytes
  • Endogenous Retroviruses*
  • Epitopes, T-Lymphocyte
  • Female
  • HLA-A2 Antigen / genetics
  • Humans
  • Immunotherapy / methods

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen