Traditional Chinese medicine in the prevention and treatment of lung cancer metastasis by regulating tumor-associated macrophages: a narrative review.

Background and Objective: Lung cancer remains the leading cause of cancer-related mortality globally, with metastasis representing the principal determinant of poor clinical outcomes. Tumor-associated macrophages (TAMs), as key components of the tumor microenvironment (TME), play pivotal roles in modulating immune responses, tumor progression, and metastatic dissemination. Traditional Chinese medicine (TCM) has demonstrated potential in regulating TAM polarization, thereby inhibiting tumor metastasis. This review aims to comprehensively summarize the current evidence on how TCM modulates TAMs to prevent and treat lung cancer metastasis. Methods: We conducted a systematic search of literature on TAMs, lung cancer metastasis, and TCM published between 2016 and 2025. Following initial screening of retrieved articles, relevant sources were cross-referenced to identify additional studies. Key Content and Findings: This review presents a comprehensive summary of recent advances in the modulation of TAMs by TCM in the setting of lung cancer metastasis. TCM-derived compounds and classical herbal prescriptions have demonstrated the ability to reprogram TAMs from an immunosuppressive M2-like phenotype to an immunostimulatory M1-like phenotype. Mechanistically, these agents exert their effects by modulating multiple signaling pathways, including TLR4/NF-κB, STAT3/STAT6, PI3K/AKT, and STING/TBK1/IRF3 pathways, as well as key cytokine networks involving interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Representative monomers, including curcumin, calycosin, and polyphyllin VII, as well as classical formulas such as Bu-Fei decoction (BFD) and Kejinyan decoction, exhibit anti-metastatic activity by reprogramming the immunosuppressive TME and enhancing anti-tumor immune responses. Conclusions: TCM represents a promising strategy for suppressing lung cancer metastasis by targeting TAMs and restoring immune homeostasis. Future research should focus on the standardization of TCM formulations, mechanistic elucidation, and translational validation in clinical settings. Integrating TCM with contemporary immunotherapies may yield synergistic benefits and advance precision oncology for metastatic lung cancer.