Department of Oncology, The Eighth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100091, China; Department of Oncology, The Fifth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100071, China.
College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing Key Laboratory of OTIR, Beijing, 100091, China.
Biomed Pharmacother. 2024 Jun;175:116609. doi: 10.1016/j.biopha.2024.116609. Epub 2024 Apr 27.
Long-term chronic stress is an important factor in the poor prognosis of cancer patients. Chronic stress reduces the tissue infiltration of immune cells in the tumor microenvironment (TME) by continuously activating the adrenergic signaling, inhibits antitumor immune response and tumor cell apoptosis while also inducing epithelial-mesenchymal transition (EMT) and tumor angiogenesis, promoting tumor invasion and metastasis. This review first summarizes how adrenergic signaling activates intracellular signaling by binding different adrenergic receptor (AR) heterodimers. Then, we focused on reviewing adrenergic signaling to regulate multiple functions of immune cells, including cell differentiation, migration, and cytokine secretion. In addition, the article discusses the mechanisms by which adrenergic signaling exerts pro-tumorigenic effects by acting directly on the tumor itself. It also highlights the use of adrenergic receptor modulators in cancer therapy, with particular emphasis on their potential role in immunotherapy. Finally, the article reviews the beneficial effects of stress intervention measures on cancer treatment. We think that enhancing the body's antitumor response by adjusting adrenergic signaling can enhance the efficacy of cancer treatment.
长期慢性应激是癌症患者预后不良的一个重要因素。慢性应激通过持续激活肾上腺素能信号，抑制抗肿瘤免疫反应和肿瘤细胞凋亡，同时诱导上皮-间充质转化（EMT）和肿瘤血管生成，促进肿瘤侵袭和转移，从而减少肿瘤微环境（TME）中免疫细胞的组织浸润。本综述首先总结了肾上腺素能信号如何通过结合不同的肾上腺素能受体（AR）异二聚体来激活细胞内信号。然后，我们重点讨论了肾上腺素能信号如何调节免疫细胞的多种功能，包括细胞分化、迁移和细胞因子分泌。此外，本文还讨论了肾上腺素能信号通过直接作用于肿瘤本身发挥促瘤作用的机制。它还强调了肾上腺素能受体调节剂在癌症治疗中的应用，特别强调了它们在免疫治疗中的潜在作用。最后，本文综述了应激干预措施对癌症治疗的有益影响。我们认为，通过调节肾上腺素能信号增强机体的抗肿瘤反应可以提高癌症治疗的疗效。
