2025/12/19 by Bin-Jin Hwang, Erika J. Crosby, David T. Severson +20 · 1 voice
Immunology and Microbiology · Medicine · #Immunotherapy and Immune Responses #Cancer Immunotherapy and Biomarkers #T-cell and B-cell Immunology
paper · doi:10.1126/sciimmunol.adz2294
openalex created_date 2025/12/19 · openalex publication_date 2025/12/19 · openalex updated_date 2026/07/30
Tumor antigen vaccination represents an appealing approach for cancer but has failed to materialize as oncologic standard of care. To understand long-term vaccine efficacy, we conducted a retrospective analysis of patients with human epidermal growth receptor 2 + (HER2 + ) breast cancer who received HER2-targeting vaccines and survived for >18 years. PBMC analysis revealed HER2-specific CD27 + memory CD4 and CD8 T cells, suggesting that CD27 signaling supports long-term immune memory. In human CD27 transgenic mice, combining HER2 vaccination with anti-CD27 agonism enhanced HER2-specific responses, particularly long-lived CD4 memory T cells. Murine models demonstrated ~40% tumor regression with combined therapy compared with vaccine alone (~6%). Additional scRNA-seq analysis identified CD4 T cells with a distinct gene expression profile, and depletion/adoptive transfer studies validated that CD4 T cells were essential for this effect. These findings suggest that CD27 agonism enhances vaccine-induced antigen-specific CD4 T cell responses, enabling durable antitumor immunity not entirely dependent on CD8 T cells.