β受体阻滞剂协助恶性肿瘤免疫治疗的研究进展

Research Progress of β-Blockers Assisting Immunotherapy for Malignant Tumors

摘要: β受体阻滞剂是传统的心血管疾病治疗药物，包括普萘洛尔、卡维地洛、阿替洛尔等。近年来，随着β肾上腺素在恶性肿瘤免疫微环境中发挥的作用的研究显露出新的发现，β受体阻滞剂在癌症治疗中的使用方式找到了新方向。在动物试验和体外实验中发现，β受体阻滞剂作为免疫治疗的协助用药，可以作用于免疫微环境，增加细胞毒性免疫细胞数量，从而达到延长和增强免疫治疗的效果，如普萘洛尔可减少癌细胞上响应干扰素γ (IFN-γ)表达的程序性死亡配体1 (PD-L1)，使得细胞毒性T淋巴细胞(CD8+T)浸润增加。在可供试验的数类药品中，β3受体阻滞剂表现出较大的潜力，β3-肾上腺素能受体参与介导从免疫活性肿瘤微环境到免疫抑制性肿瘤微环境的转变，因此β3-肾上腺素能受体阻断可减少肿瘤的生长，从而诱导免疫耐受的逆转。但是此类效果受到多种因素的影响，主要是肿瘤类型的不同，临床实践的效果仍需进一步探索。

Abstract: Beta-blockers are traditional cardiovascular disease treatment drugs, including propranolol, carvedilol, atenolol and so on. In recent years, with the discovery of new research on the role of β-epinephrine in the immune microenvironment of malignant tumors, the use of β-blockers in cancer treatment has found a new direction. It has been found in animal experiments and in vitro experiments that beta-blockers, as adjuvant drugs for immunotherapy, can act on the immune microenvironment and increase the number of cytotoxic immune cells, thereby prolonging and enhancing the effects of immunotherapy. Propranolol, for example, reduces PD-L1 on cancer cells in response to IFN-γ expression, resulting in increased CD8 T cell infiltration. Among the several classes of drugs available for testing, β3-receptor blockers show greater potential. β3-adrenergic receptors are involved in mediating the transition from the immunoreactive tumor microenvironment to the immunosuppressive tumor microenvironment, so β3-adrenergic receptor blocking can reduce tumor growth and induce reversal of immune tolerance. Thus, the effect of immunotherapy can be prolonged and enhanced, but its effect is affected by many factors, mainly the different tumor types, and the effect of clinical practice still needs to be further explored.