Mountain-Cultivated Ginseng in Combination with Acupuncture Inhibits Breast Cancer Growth via PD-1/PD-L1 Degradation Mediated by AMPK-Induced Autophagy

Immunotherapy has recently garnered more attention in the treatment of breast cancer. Ginseng has been extensively utilized in immunomodulation. Acupuncture is acknowledged as an effective adjunctive therapy for treating various cancers through the modulation of the immune system. Nonetheless, the extent to which the combination of ginseng and acupuncture exerts an enhanced anti-tumor effect in breast cancer treatment remains unclear. This study assessed the impact of mountain-cultivated ginseng in conjunction with acupuncture on the anti-tumor immune response in breast cancer in a 4T1 xenograft BALB/c mouse model. The findings indicated acupuncture, when paired with mountain-cultivated ginseng, could augment the suppression of tumor growth. Acupuncture in conjunction with ginseng therapy enhanced the immunological activity of CD8⁺ cytotoxic T cells by elevating the numbers of IFN-γ⁺/CD8⁺ T cells and TNF-α⁺/CD8⁺ T cells, along with the release of many pro-inflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ). Furthermore, it was established that acupuncture in conjunction with ginseng therapy facilitated the degradation of PD-L1 and PD-1 <i>via</i> the Sirt1/AMPK-mediated autophagy pathway. This study revealed that the combination of acupuncture and ginseng treatment augmented the suppression of PD-1/PD-L1 immune checkpoint, hence amplifying the anti-tumor immune response and offering a potential method for breast cancer therapy.