Synergistic Antitumor Effects of Caerin Peptides and Dendritic Cell Vaccines in a 4T-1 Murine Breast Cancer Model

<b>Background/Objectives</b>: Breast cancer remains a leading cause of cancer-related mortality among women worldwide, necessitating novel therapeutic strategies. This study aimed to investigate the synergistic antitumor effects of caerin peptides (F1/F3) combined with dendritic cell (DC) vaccines in a 4T-1 murine breast cancer model, providing new insights for breast cancer immunotherapy. <b>Methods</b>: In vitro experiments evaluated the effects of F1/F3 on 4T-1 cell proliferation and apoptosis. A 4T-1 breast cancer mouse model was established, and treatments included F1/F3 alone, DC vaccines (DCV₁: loaded with whole tumor antigens; DCV₂: loaded with F1/F3-induced apoptotic antigens), or combination therapy. Flow cytometry analyzed immune cell subsets in the tumor microenvironment and lymph nodes, while ELISA measured cytokine levels. <b>Results</b>: F1/F3 significantly inhibited 4T-1 cell proliferation and induced apoptosis while suppressing tumor growth and lung metastasis in vivo. Flow cytometry revealed increased infiltration of CD4⁺ T cells and cDC₁ in tumors, along with reduced PD-L1 expression. DCV₂ exhibited stronger T-cell proliferation induction and lower IL-10 secretion in vitro. Combination therapy with DCV₂ and F1/F3 demonstrated superior tumor suppression compared to monotherapy. <b>Conclusions</b>: F1/F3 enhances antitumor immunity by modulating the tumor microenvironment, and its combination with DCV₂ yields synergistic effects. This study provides experimental evidence for combination immunotherapy in breast cancer, with potential for further optimization of DC vaccine design to improve efficacy.