Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
Int J Mol Sci. 2023 Aug 16;24(16):12837. doi: 10.3390/ijms241612837.
The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of the tumor microenvironment, nor-adrenaline (NA) is poured in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surfaces of cancer and immune cells and are often involved in the activation of pro-tumoral signaling pathways. Beta2-adrenergic receptors (β2-ARs) are an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate regulatory immune cells and inhibit effector immune cells. Blocking β2-AR increases activation, proliferation, and cytokine release of T lymphocytes. Moreover, β2-AR deficiency during metabolic reprogramming of T cells increases mitochondrial membrane potential and biogenesis. In the view of the available research data, the immunosuppressive role of β2-AR in T cells presents it as a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged the contemporary knowledge about adrenergic-stress-mediated β2-AR activation on T lymphocytes inside tumor milieu.
大多数肿瘤的微环境较为复杂，包含许多免疫抑制方面。一些研究表明，儿茶酚胺系统对控制免疫反应至关重要。在肿瘤微环境中，去甲肾上腺素（NA）由神经支配的神经和肿瘤组织本身分泌。去甲肾上腺素的受体存在于癌症和免疫细胞的表面，并且经常参与激活促肿瘤信号通路。β2-肾上腺素能受体（β2-AR）是一类新兴的受体，能够调节免疫细胞的功能。β2-AR 被报道能激活调节性免疫细胞并抑制效应性免疫细胞。阻断β2-AR 会增加 T 淋巴细胞的激活、增殖和细胞因子释放。此外，T 细胞代谢重编程期间β2-AR 缺乏会增加线粒体膜电位和生物发生。根据现有研究数据，β2-AR 在 T 细胞中的免疫抑制作用使其成为 CAR-T 细胞疗法中一个可靶向的检查点。在这篇综述中，我们简要介绍了肿瘤微环境中儿茶酚胺应激介导的β2-AR 激活对 T 淋巴细胞的当代认识。
