Social isolation promotes tumor immune evasion via β2-adrenergic receptor

Abstract

Social isolation is a recognized risk factor for tumor initiation and mortality, but the role and mechanisms responsible for social isolation on tumor progression are poorly understood. In this study, we found that social isolation contributed to accelerated tumor growth and induced a remodeling of the tumor immune microenvironment, resulting in immunosuppression. Mechanistically, social isolation triggered the activation of the sympathetic nervous system, leading to impaired CD8⁺ T cell antitumor immune responses by activating β-adrenergic receptor 2 (β2-AR), which highly expressed on tumor-infiltrating CD8⁺ T cells. Pharmacological inhibition of β2-AR signaling effectively enhanced CD8⁺ T cell anti-tumor immune responses and improved the efficacy of anti-PD-1 immunotherapy in the context of social isolation. Thus, our study uncovers a mechanism through which social isolation induces tumor immune evasion and offers potential directions for cancer immunotherapy in socially isolated patients.

Keywords: CD8(+) T cells; Norepinephrine; Social isolation; Sympathetic nervous system; β-adrenergic receptor 2.