Electroacupuncture regulates inflammatory cytokines by activating the vagus nerve to enhance antitumor immunity in mice with breast tumors
Zhiyun Zhang, Qing-Quan Yu, Xiao-Ning Zhang, Xiaoyu Wang, Yang‐Shuai Su, Wei He, Jie Li, Ye Wan, Xiang‐Hong Jing
Abstract
The aim of this study was to explore the potential effect of electroacupuncture (EA) at ST36 on mice bearing breast tumors by regulating inflammatory cytokines to enhance antitumor immunity via vagus nerve. Female BALB/c mice were implanted with 4T1-luc2 breast tumor cells to establish a murine mammary cancer model. Tumor growth was evaluated by tumor volume, weight and bioluminescence imaging. Inflammatory conditions in serum and tumor tissue were assessed by cytokines (IL-1β, TNF-α and IL-10) and HE staining. Proportions and functions of CD8+ T cells, NK cells and MDSCs were identified by flow cytometry and western blot. Involvement of vagal efferent components was confirmed by ChAT and c-Fos double labeling immunohistochemistry in dorsal motor nucleus of vagus (DMV). Subdiaphragmatic vagotomy was employed to determine if the effect of EA was mediated by vagus nerve. EA at ST36 reduced the volume and weight of tumors within 22 days after implantation. Proinflammatory cytokines IL-1β and TNF-α in serum, tumor and local inflammatory infiltration were obviously attenuated after EA. Meanwhile, EA intervention significantly augmented the proportion and cytolytic function of CD8+ T cells and NK cells, along with a decline in the accumulation and immunosuppressive activities of MDSCs. Finally, c-Fos expression in ChAT+ neurons in DMV increased following EA, and the ameliorating effect of EA was obviously blocked by subdiaphragmatic vagotomy. EA intervention relieved tumor progression in breast tumor-bearing mice by alleviating inflammation and enhancing antitumor immunity, which was mediated by eliciting efferent vagus nerve activity.