Electroacupuncture enhances CD8+ T cells recruitmentmodulating sympathetic nervous system to suppress tumor growth in mice bearing triple-negative breast cancer.

OBJECTIVE: To investigate whether peritumoral electroacupuncture (EA) suppresses tumor growth viaCD8+ T cell infiltration mediated by sympathetic nervous system (SNS) regulation. METHODS: Utilizing a mouse model of triple-negative breast cancer (TNBC), the SNS was activated through chronic restraint stress (CRS); chemical sympathetic denervation was induced by 6-hydroxydopamine (6-OHDA). The anti-tumor and immune regulatory effects of EA were evaluated by multidimensional methods, including in vivobioluminescence imaging, flow cytometry, immunofluorescence, and enzyme-linked immunosorbent assay. RESULTS: Peritumoral EA decreased the volume and weight of tumors within 22 d after the implantation. Intratumoral CD8+ T cells significantly increased after EA. C-C motif chemokine ligand 5, as a chemokine that recruits effector T cells to the tumor microenvironment, also up-regulated. Meanwhile, EA reduced intratumoral sympathetic innervation and norepinephrine level. Subsequently, we found CRS significantly accelerates tumor growth and reduces the density of CD8+ T cell infiltration. However, EA reversed the tumor-promoting effect and immune suppression caused by CRS effectively. Furthermore, chemical sympathetic ablation with 6-OHDA revealed that the anti-tumor effect of EA was dependent on sympathetic integrity, as the ablation impaired both tumor-suppressing effect and CD8+ T cell recruitment mediated by EA. CONCLUSION: EA enhances anti-tumor immunity through SNS emphasizing the effective remodeling of the tumor immune microenvironment in mice with TNBC by neuro-immune interactions.