Acupuncture Potentiates anti-PD-1 Efficacy by Promoting CD5+ Dendritic Cells and T Cell-Mediated Tumor Immunity in a Mouse Model of Breast Cancer.

Abstract

Acupuncture has been recognized as a complementary therapy for various malignancies by modulating immune responses. However, the impact of acupuncture on the antitumor immune efficacy of PD-1 inhibitors remains unclear. This study evaluates the effectiveness of acupuncture in conjunction with PD-1 inhibitors in enhancing the antitumor immune response against breast cancer and elucidates the potential molecular mechanisms through RNA-Seq transcriptome analysis in a 4T1 xenograft BALB/c mouse model of breast cancer. The findings indicate that the combination of acupuncture and PD-1 inhibitors significantly impedes tumor development by promoting tumor cell apoptosis and inhibiting tumor growth, angiogenesis, and metastasis. RNA-Seq analysis revealed that differentially expressed genes following acupuncture intervention were primarily enriched in immune response pathways, T cell activation, and cytokine interactions, including immune cell-related CD genes such as CD5, CD4, and CD8. Notably, acupuncture stimulation enhanced CD5 expression, which correlated positively with overall survival in breast cancer patients. Furthermore, the combination treatment led to improved immunity characterized by an increase in CD5⁺ dendritic cells, as well as CD4⁺ and CD8⁺ T cell populations, alongside elevated serum levels of various cytokines (IL-2, IL-6, TNF-α, IFN-γ). Collectively, this study demonstrates that acupuncture intervention enhances the antitumor immune response associated with PD-1 inhibitors, suggesting a promising therapeutic approach for immune checkpoint inhibitor therapy in breast cancer.