Tao Zhang, Junsong Zeng, Xue Li, Yannan Wang, Xuejiao Han
Lung cancer TAM research has moved from descriptive phenotyping toward mechanisms of heterogeneity, metabolism, and chemokine-driven immune regulation. Immunotherapy combinations and spatial technologies are current frontiers, but translational bottlenecks persist: lack of standardized TAM subset nomenclature, limited clinical validation, and neglect of small cell lung cancer. Cross-institutional collaboration and rigorous clinical testing are needed to bridge the gap between mechanistic discovery and patient benefit.
BACKGROUND: Tumor-associated macrophages (TAMs) play a critical role in lung cancer progression, immune evasion, and treatment resistance within the unique, tissue-specific pulmonary immune microenvironment. However, a comprehensive bibliometric synthesis combining multi-database validation, quantitative time-series forecasting, and clinical translation integration remains lacking in the literature.
METHODS: Following a PRISMA-compliant two-stage screening protocol, literature published between 2005 and 2025 was retrieved from the Web of Science Core Collection (WOSCC) and Scopus. Bibliometric mapping and keyword clustering were performed using VOSviewer (v1.6.20), CiteSpace (v7.0.0), and Bibliometrix (v4.1.2). Predictive modeling of future annual output was conducted using an Auto-Regressive Integrated Moving Average (ARIMA) time-series framework. Methodological quality and network integrity were evaluated using CiteSpace structural metrics (Modularity Q and Mean Silhouette S).
RESULTS: Annual output increased slowly from 2005 to 2015 and accelerated sharply after 2018, reaching 439 articles in 2025, and is projected to reach 455 articles (95% CI 428-482) in 2026. China led in publication volume (1,970 articles in WOSCC) while the United States had the highest citation impact. Keyword clustering revealed a thematic progression from early genetic susceptibility and chemotherapy-related studies, through TAM polarization and metabolic reprogramming, to recent emphasis on lung adenocarcinoma, immune infiltration, and immunotherapy combinations. Citation bursts highlighted PD-1 expression on TAMs and recent interest in macrophage polarization. Fragmentary clusters on sarcopenia and animal models suggest underdeveloped but clinically relevant niches. Major funding came from the National Natural Science Foundation of China and the US National Cancer Institute.
CONCLUSIONS: Lung cancer TAM research has moved from descriptive phenotyping toward mechanisms of heterogeneity, metabolism, and chemokine-driven immune regulation. Immunotherapy combinations and spatial technologies are current frontiers, but translational bottlenecks persist: lack of standardized TAM subset nomenclature, limited clinical validation, and neglect of small cell lung cancer. Cross-institutional collaboration and rigorous clinical testing are needed to bridge the gap between mechanistic discovery and patient benefit.