Grain-sized moxibustion activates dendritic cells to enhance the antitumor immunity of cancer vaccines.

Background: Moxibustion, a traditional Chinese medicine (TCM) therapy, employs thermal stimulation from the combustion of Artemisia argyi H.Lév. & Vaniot at acupoints to treat "deficiency-cold syndromes" (xuhan zheng), historically linked to immune dysfunction and chronic inflammation. Modern pharmacological studies showed that grain-sized moxibustion (gM) enhances innate immune surveillance such as natural killer (NK) cell recruitment. However, its synergy with vaccine-induced adaptive immunity remains unexplored. Guided by the TCM principle of fu zheng qu xie ("fortify the host to dispel pathogens"), this study investigated whether gM augments cancer vaccine efficacy and validate the mechanistic basis of thermal acupoint stimulation in amplifying adaptive antitumor immunity.

Methods: In tumor-bearing mice model, gM was applied to the ST36 (Zusanli) acupoint. Adjuvant effects on the cancer vaccine were evaluated through flow cytometry, β-adrenergic receptor blockade, and cell depletion.

Results: gM synergized with the cancer vaccine, significantly suppressing tumor growth. Mechanistically, gM inhibited β-adrenergic signaling, driving DC maturation and subsequent coordination of CD4⁺ T cell, CD8⁺ T cell and NK cell responses. CD4⁺ T cells as primary effectors, with NK cells playing a secondary role. Propranolol mirrored gM's effects, further enhancing DC activation and tumor suppression when combined with vaccination.

Conclusion: Both gM and β-blockers enhance cancer vaccine efficacy through β-adrenergic suppression and maturation of DC. These findings mechanistically bridge TCM's fu zheng qu xie strategy with modern immunotherapy, positioning β-adrenergic modulation as a convergent target for traditional and pharmacological interventions.