Identification of immunogenic HLA-A*02:01 epitopes associated with HCC for immunotherapy development

作者：Anthony Maino, Ekaterina Bourova-Flin, Thomas Decaens, Saadi Khochbin, Zuzana Macek Jílková, Sophie Rousseaux, Joël Plumas, Philippe Saas, Laurence Chaperot, Olivier Manches · 发表于：Hepatology Communications · 年份：2025 · DOI：10.1097/hc9.0000000000000659 · 被引用次数：4 · 研究领域：Immunotherapy and Immune Responses、vaccines and immunoinformatics approaches、Cancer Immunotherapy and Biomarkers

BACKGROUND: HCC is the most common form of primary liver cancer, and despite recent advances in cancer treatment, it remains associated with poor prognosis and a lack of response to conventional therapies. Immunotherapies have emerged as a promising approach for cancer treatment, especially through the identification of tumor-specific immunogenic epitopes that can trigger a targeted immune response. This study aimed to identify immunogenic epitopes associated with HCC for the development of specific immunotherapies. METHODS: We used high-throughput data screening and bioinformatics tools for antigens and epitope selection. The immunogenicity of the selected epitopes was studied after coculture of peripheral blood mononuclear cells obtained from healthy donors or HCC patients with a plasmacytoid dendritic cell line loaded with the selected peptides. Specific CD8+ T cell amplification and functionality were determined by labeling with tetramers and by IFN-γ and CD107a expression (flow cytometry and ELISpot). RESULTS: We analyzed the transcriptional gene expression landscape of HCC to screen for a set of 16 ectopically expressed genes in a majority of HCC samples. Epitopes predicted to bind to HLA-A*02:01 with high affinity were further validated for their immunogenicity using the previously described plasmacytoid dendritic cell line in ex vivo CD8+ activation assays using patient immune cells. Three out of the 30 tested epitopes, namely FLWGPRALV (MAGE-A3), FMNKFIYEI (AFP), and...