Social isolation promotes tumor immune evasion via β2-adrenergic receptor

IF 8.8 2区 医学 Q1 IMMUNOLOGY
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引用次数: 0

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.
社会隔离通过β2-肾上腺素能受体促进肿瘤免疫逃避
社会隔离是公认的肿瘤发生和死亡的风险因素,但社会隔离对肿瘤进展的作用和机制却鲜为人知。在这项研究中,我们发现社会隔离会加速肿瘤生长,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,社会隔离会引发交感神经系统的激活,通过激活肿瘤浸润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。药理抑制β2-AR信号传导可有效增强CD8+ T细胞的抗肿瘤免疫反应,并提高抗PD-1免疫疗法在社会隔离背景下的疗效。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疗法提供了潜在的方向。
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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