Adrenergic Regulation of Cancer Immunity.

Beta-adrenergic receptor signaling is linked to immune suppression in the tumor microenvironment, while beta-blocker use is associated with survival benefits across cancers in studies totaling over 600,000 patients.

• Why it matters: Neuro-immune cross-talk shapes both tumor progression and how patients respond to therapy, yet the specific adrenergic pathways that regulate antitumor immunity need clearer therapeutic mapping.
• What they did: This review synthesizes evidence on distinct roles of beta- and alpha-2 adrenergic receptor signaling, including retrospective patient analyses and meta-analyses, plus preclinical tests of alpha-2-AR agonists in immunocompetent murine models.
• The result: Beta-AR signaling impairs dendritic cell cross-presentation and CD8+ T-cell/NK function, promotes T-cell exhaustion, and increases regulatory-T and myeloid-derived suppressor activity; alpha-2-AR agonists induce antitumor immunity in checkpoint-resistant tumors via CD4+ and CD8+ T-cell–dependent mechanisms.

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