Ammons Dylan T, MacDonald Cameron R, Chow Lyndah, Repasky Elizabeth A, Dow Steven
Flint Animal Cancer Center, Fort Collins, Colorado, USA.
Department of Microbiology, Immunology, and Pathology, Fort Collins, Colorado, USA.
Vet Comp Oncol. 2023 Jun;21(2):159-165. doi: 10.1111/vco.12891. Epub 2023 Mar 23.
Recent studies have highlighted a key role played by the sympathetic nervous system (SNS) and adrenergic stress in mediating immune suppression associated with chronic inflammation in cancer and other diseases. The connection between chronic SNS activation, adrenergic stress and immune suppression is linked in part to the ability of catecholamines to stimulate the bone marrow release and differentiation of myeloid-derived suppressor cells (MDSC). Rodent model studies have revealed an important role for β-adrenergic receptor signalling in suppression of cancer immunity in mice subjected to chronic stresses, including thermal stress. Importantly, therapeutic blockade of beta-adrenergic responses by drugs such as propranolol can partially reverse the generation and differentiation of MDSC, and partly restore tumour immunity. Clinical trials in both humans and dogs with cancer have demonstrated that propranolol blockade can improve responses to radiation therapy, cancer vaccines and immune checkpoint inhibitors. Thus, the SNS stress response has become an important new target to relieve immune suppression in cancer and other chronic inflammatory conditions.
最近的研究突出了交感神经系统（SNS）和肾上腺素能应激在介导与癌症及其他疾病中的慢性炎症相关的免疫抑制方面所起的关键作用。慢性SNS激活、肾上腺素能应激与免疫抑制之间的联系，部分与儿茶酚胺刺激骨髓释放和髓源性抑制细胞（MDSC）分化的能力有关。啮齿动物模型研究表明，β-肾上腺素能受体信号传导在遭受包括热应激在内的慢性应激的小鼠的癌症免疫抑制中起重要作用。重要的是，通过普萘洛尔等药物对β-肾上腺素能反应进行治疗性阻断，可以部分逆转MDSC的生成和分化，并部分恢复肿瘤免疫。针对患有癌症的人类和犬类的临床试验表明，普萘洛尔阻断可以改善对放射治疗、癌症疫苗和免疫检查点抑制剂的反应。因此，SNS应激反应已成为缓解癌症和其他慢性炎症性疾病中免疫抑制的一个重要新靶点。
