社会隔离是公认的肿瘤发生和死亡的危险因素，但人们对社会隔离在肿瘤进展中的作用和机制知之甚少。在这项研究中，我们发现社会隔离有助于加速肿瘤生长并诱导肿瘤免疫微环境的重塑，从而导致免疫抑制。从机制上讲，社会隔离触发了交感神经系统的激活，通过激活在肿瘤浸润性 CD8 T 细胞上高表达的 β-肾上腺素能受体 2 (β2-AR)，导致 CD8 T 细胞抗肿瘤免疫反应受损。 β2-AR信号传导的药理学抑制有效增强了CD8 T细胞抗肿瘤免疫反应，并提高了社会隔离背景下抗PD-1免疫治疗的疗效。因此，我们的研究揭示了社会隔离诱导肿瘤免疫逃避的机制，并为社会隔离患者的癌症免疫治疗提供了潜在的方向。版权所有 © 2024 Elsevier Inc. 保留所有权利。

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.Copyright © 2024 Elsevier Inc. All rights reserved.