SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1635331
This article is part of the Research TopicNeural influences on tumor immunity: Exploring neuroimmunology in cancerView all 6 articles
Impact of Beta Blockers on Cancer Neuroimmunology: A Systematic Review and Meta-analysis of Survival Outcomes and Immune Modulation
Provisionally accepted
- 1University of Chinese Academy of Social Sciences, Beijing, China
- 2University of Nanking, Nanjing, China
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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
Keywords: beta-blockers, cancer neuroimmunology, immune checkpoint inhibitors, Tumor Microenvironment, Meta-analysis
Received: 26 May 2025; Accepted: 03 Jul 2025.
Copyright: © 2025 Zhang, Liu, Ren and Xi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuan Xi, University of Nanking, Nanjing, China
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