Current Research Status and Molecular Mechanisms of Traditional Chinese Medicine Combined with Anti-Tumor Therapy Targeting Tumor-Associated Macrophages

Abstract

Tumor-associated macrophages (TAMs) are a key component of the tumor immune microenvironment, and their function depends on their polarization state. M1 macrophages are generally associated with anti-tumor immune activity, while M2 macrophages are linked to immunosuppression, tumor progression, and metastasis. Recent studies have shown that Traditional Chinese Medicine (TCM) may regulate TAM polarization in cancer. Both experimental and clinical evidence suggest that TCM monomers and formulas can influence this process, although the strength of evidence varies. Compounds such as artesunate, matrine, and celastrol may shift macrophages toward the M1 phenotype, involving pathways including PI3K/Akt/mTOR, STAT6, and NF-κB. TCM formulas such as Bufei Decoction and Danggui Buxue Decoction have also been reported to enhance chemotherapy or immunotherapy effects, possibly through reducing immunosuppressive interactions in the tumor microenvironment. Clinically, Jianpi Yangzheng Xiaozhong Decoction has shown potential survival benefits in gastric cancer and has been included in integrated treatment guidelines. However, current evidence remains limited, with issues such as small sample sizes and lack of standardization. In addition, poor bioavailability of some TCM components continues to limit clinical application. Overall, TCM may regulate TAM polarization and reshape the tumor immune microenvironment through multiple targets, but further well-designed clinical studies are still needed for translation into practice.