Zhang Fangyuan, Wang Yu, Liu Feng, Li Yixian, Liu Xinxin, Ren Xueying, Yuan Xi
Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Front Immunol. 2025 Aug 6;16:1635331. doi: 10.3389/fimmu.2025.1635331. eCollection 2025.
Emerging evidence suggests that beta-blockers (BBs) may influence cancer progression by modulating the neuroimmune axis. However, clinical findings remain heterogeneous, necessitating a comprehensive evaluation of their impact on survival outcomes and immune modulation across malignancies.
We conducted a systematic review and meta-analysis following PRISMA guidelines, analyzing 79 studies from PubMed, Embase, and Web of Science. Pooled hazard ratios (HRs) for overall survival (OS) and cancer-specific survival (CSS) were calculated using random-effects models. Subgroup analyses explored effects by cancer type, BB class (non-selective vs. β1-selective), and concurrent immunotherapy. Immune biomarkers (e.g., PD-L1 expression, tumor-infiltrating lymphocytes) were qualitatively synthesized.
BB use showed no significant overall effect on CSS (HR = 0.97, 95% CI: 0.92-1.02) but exhibited substantial heterogeneity (I² = 80%). Protective associations were observed in breast cancer (HR = 0.27-0.50) and melanoma, while detrimental effects emerged in pancreatic and head/neck cancers (HR > 1.0). Clinically, BBs combined with immune checkpoint inhibitors (ICIs) improved survival (HR=0.91, 95% CI: 0.85-0.98), particularly in PD-L1+ tumors (OR=1.29 for enhanced expression). Non-selective BBs showed stronger immune modulation (CD8+ T-cell SMD=0.49 vs 0.22 for β1-selective).
BBs demonstrate clinically meaningful benefits when combined with immunotherapy (HR=0.91) particularly in β2-AR+ melanoma and breast cancer, but show potential harm in pancreatic/head-neck cancers (HR>1.0). These results support preferential use of propranolol (20-40mg/day) in immunotherapy-treated melanoma, and avoidance of routine BB use in non-immunogenic tumors without adrenergic profiling. Prospective trials should validate these selection criteria.
新出现的证据表明，β受体阻滞剂（BBs）可能通过调节神经免疫轴影响癌症进展。然而，临床研究结果仍然存在异质性，因此有必要全面评估其对各种恶性肿瘤生存结局和免疫调节的影响。
我们按照PRISMA指南进行了系统评价和荟萃分析，分析了来自PubMed、Embase和Web of Science的79项研究。使用随机效应模型计算总生存（OS）和癌症特异性生存（CSS）的合并风险比（HRs）。亚组分析探讨了癌症类型、BB类别（非选择性与β1选择性）和同时进行免疫治疗的影响。对免疫生物标志物（如PD-L1表达、肿瘤浸润淋巴细胞）进行了定性综合分析。
使用BBs对CSS没有显著的总体影响（HR = 0.97，95%CI：0.92 - 1.02），但存在显著异质性（I² = 80%）。在乳腺癌（HR = 0.27 - 0.50）和黑色素瘤中观察到了保护作用，而在胰腺癌和头颈癌中出现了有害影响（HR > 1.0）。临床上，BBs与免疫检查点抑制剂（ICIs）联合使用可改善生存（HR = 0.91，95%CI：0.85 - 0.98），特别是在PD-L1阳性肿瘤中（表达增强的OR = 1.29）。非选择性BBs显示出更强的免疫调节作用（CD8 + T细胞标准化均数差为0.49，而β1选择性为0.22）。
BBs与免疫治疗联合使用时显示出具有临床意义的益处（HR = 0.91），特别是在β2-AR阳性的黑色素瘤和乳腺癌中，但在胰腺癌/头颈癌中显示出潜在危害（HR > 1.0）。这些结果支持在接受免疫治疗的黑色素瘤中优先使用普萘洛尔（20 - 40mg/天），并避免在未经肾上腺素能分析的非免疫原性肿瘤中常规使用BBs。前瞻性试验应验证这些选择标准。
