In vivo antitumor activity of dendritic cell-vaccinated skin flap model for mouse breast cancer

Abstract Despite advances in immune checkpoint inhibitor (ICI) therapy, managing locally advanced breast cancer remains a major challenge in clinical oncology. Our previous study introduced a dendritic cell (DC)-based skin-flap vaccination strategy using a rat model. The aim of this study was to establish a mouse immune-flap vaccination model targeting breast cancer and to evaluate its antitumor efficacy with or without ICI therapy. Mature DCs were generated from mouse bone marrow cells stimulated with tumor lysates and lipopolysaccharide. DC migration to regional lymph nodes was assessed 24 h after injection of labeled DCs into the skin flap using flow cytometry. In the DC vaccination experiment, immune cell subpopulations within tumors and antitumor effects were evaluated using flow cytometry and enzyme-linked immunospot assays after four weekly DC injections. Injected DCs successfully migrated to regional lymph nodes 24 h post-injection. Both the DC vaccine and anti-PD-1 antibody groups demonstrated potent antitumor effects in vivo , achieving over 50% tumor size reduction. However, the combination treatment exhibited a markedly weaker response. Tumor-infiltrating lymphocyte analysis demonstrated that the levels of CD4 + memory T cells, macrophages, and B cells increased in the DC vaccine group, CD8 + effector T cell levels increased in the anti-PD-1 antibody group, and tumor-infiltrating immune cell levels significantly decreased in the combination group. These findings highlight the potential of immune flap-based vaccination as a novel immunotherapeutic strategy. However, the diminished efficacy observed with combination therapy emphasizes the need to optimize treatment regimens.