To mechanistically understand better vaccine efficacy, Hwang et al. conducted a retrospective analysis of long-term (>18 years) breast cancer survivors who received HER2+ targeted autologous DC vaccines. PBMC analysis revealed that all patients had persistent CD27+ HER2-specific memory CD4+ and CD8+ T cells, suggesting a key role for CD27 in supporting long-term immune memory. In human-CD27-transgenic mice, primary HER2 vaccination combined with an agonist anti-CD27 mAb expanded HER2-specific CD27+ memory T cell populations in the TME and boosted antitumor responses. CD4+ (but not CD8+) T cells were essential for agonist CD27 efficacy.
Contributed by Katherine Turner
ABSTRACT: 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.
Author Info: (1) Department of Surgery, Duke University, Durham, NC, USA. (2) Department of Surgery, Duke University, Durham, NC, USA. Department of Integrative Immunobiology, Duke University,
Author Info: (1) Department of Surgery, Duke University, Durham, NC, USA. (2) Department of Surgery, Duke University, Durham, NC, USA. Department of Integrative Immunobiology, Duke University, Durham, NC, USA. (3) Department of Surgery, Duke University, Durham, NC, USA. (4) Department of Surgery, Duke University, Durham, NC, USA. (5) Department of Surgery, Duke University, Durham, NC, USA. (6) Department of Surgery, Duke University, Durham, NC, USA. (7) Department of Surgery, Duke University, Durham, NC, USA. (8) Department of Surgery, Duke University, Durham, NC, USA. (9) Department of Surgery, Duke University, Durham, NC, USA. (10) Department of Surgery, Duke University, Durham, NC, USA. (11) Department of Surgery, Duke University, Durham, NC, USA. (12) Department of Surgery, Duke University, Durham, NC, USA. Department of Pathology, Duke University, Durham, NC, USA. (13) Department of Surgery, Duke University, Durham, NC, USA. (14) Department of Surgery, Duke University, Durham, NC, USA. (15) Department of Medicine, Duke University, Durham, NC, USA. (16) Department of Surgery, Duke University, Durham, NC, USA. (17) School of Medicine, Duke University, Durham, NC, USA. (18) Department of Surgery, Duke University, Durham, NC, USA. (19) Department of Surgery, Duke University, Durham, NC, USA. (20) Celldex Therapeutics Inc., Hampton, NJ, USA. (21) Celldex Therapeutics Inc., Hampton, NJ, USA. (22) Department of Surgery, Duke University, Durham, NC, USA. Department of Integrative Immunobiology, Duke University, Durham, NC, USA. Department of Pathology, Duke University, Durham, NC, USA. (23) Department of Surgery, Duke University, Durham, NC, USA. Department of Integrative Immunobiology, Duke University, Durham, NC, USA. Department of Pathology, Duke University, Durham, NC, USA.
