PARProceedings of Anticancer Research2208-35452208-3553Bio-Byword Scientific Publishing Pty. Ltd.10.26689/par.v10i4.15853ArticleCurrent Research Status and Molecular Mechanisms of Traditional Chinese Medicine Combined with Anti-Tumor Therapy Targeting Tumor-Associated Macrophageshttps://artdesignp.com/journal/PAR/10/4/10.26689/par.v10i4.15853XuXiao’ao,LiChuang20261042026-08-11Tumor-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.

Zhang J, Gao J, Cui J, Roman M, Nicoli S, 2022, Tumor-Associated Macrophages in Tumor Progression and the Role of Traditional Chinese Medicine in Regulating TAMs to Enhance Antitumor Effects. Frontiers in Immunology, 13: Article 1026898.

Li W, Yuan Q, Li M, Yang S, 2024, Research Advances on Signaling Pathways Regulating the Polarization of Tumor-Associated Macrophages in Lung Cancer Microenvironment. Frontiers in Immunology, 15: Article 1452078.

Tu X, An B, Qi H, Zhang N, Liu Y, 2025, Traditional Chinese Medicine in the Prevention and Treatment of Lung Cancer Metastasis by Regulating Tumor-Associated Macrophages: A Narrative Review. Translational Lung Cancer Research, 14(6): 2281–2295.

Lian YF, Yang HT, Sun Y, et al., 2023, Prevention and Treatment of Lung Cancer by Regulating Tumor-Associated Macrophages with Traditional Chinese Medicine. China Journal of Chinese Materia Medica, 48(8): 2000–2009.

Chen YN, Bi L, Luo HJ, et al., 2019, Water Extract of Ginseng and Astragalus Regulates Macrophage Polarization and Synergistically Enhances DDP’s Anticancer Effect. Journal of Ethnopharmacology, 232: 11–20.

Yuan M, Zou X, Liu S, et al., 2020, Modified Jian-Pi-Yang-Zheng Decoction Inhibits Gastric Cancer Progression via the Macrophage Immune Checkpoint PI3Kgamma. Biomedicine & Pharmacotherapy, 129: Article 110440.

Zhao M, Zhou L, Zhang Q, et al., 2025, Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth. Advanced Science, 12(10): Article e2407900.

Zhao B, Hui X, Wang J, et al., 2021, Matrine Suppresses Lung Cancer Metastasis via Targeting M2-Like Tumour-Associated Macrophages Polarization. American Journal of Cancer Research, 11(9): 4308–4328.

Yang X, Wu M, Yan X, Zhang C, Luo Y, Yu J, 2023, Pulsatilla Saponins Inhibit Experimental Lung Metastasis of Melanoma via Targeting STAT6-Mediated M2 Macrophages Polarization. Molecules, 28(9): Article 3824.

Peng S, Liu Z, Song Z, et al., 2025, Vinegar-Processed Frankincense Extracts Alleviate Colorectal Cancer by Butyric Acid Mediating M1 Tumor-Associated Macrophage Pyroptosis. Chinese Medicine, 20(1): Article 208.

Bi Q, Wang M, Luo L, et al., 2025, Wenxia Changfu Formula Inhibits NSCLC Metastasis by Halting TAMs-Induced Epithelial-Mesenchymal Transition via Antagonistically Modulating CCL18. Chinese Journal of Natural Medicines, 23(7): 838–847.

Wang Z, Zhou X, Guo Y, et al., 2026, Integrating Network Pharmacology and Metabolomics to Explore the Mechanism of Xihuang Pill in Exerting Anti-Tumor Immune Effects Against Pancreatic Ductal Adenocarcinoma. Journal of Ethnopharmacology, 356: Article 120788.

Hu Y, Tang J, Sun H, et al., 2025, Artesunate Modulates the Tumor Microenvironment via STAT1/IRF1-Mediated TAM Repolarization and T Cell Activation in Non-Small Cell Lung Cancer. Phytomedicine, 146: Article 157085.

Zhan X, Xu X, Zhang P, et al., 2023, Crude Polysaccharide from Danggui Buxue Decoction Enhanced the Anti-Tumor Effect of Gemcitabine by Remodeling Tumor-Associated Macrophages. International Journal of Biological Macromolecules, 242(Pt 4): Article 125063.

Pang L, Han S, Jiao Y, Jiang S, He X, Li P, 2017, Bu Fei Decoction Attenuates the Tumor-Associated Macrophage-Stimulated Proliferation, Migration, Invasion and Immunosuppression of Non-Small Cell Lung Cancer, Partially via IL-10 and PD-L1 Regulation. International Journal of Oncology, 51(1): 25–38.

Leng M, Jiang H, Lan H, et al., 2025, Immunoregulatory Function and Anticancer Effects of Polygonatum sibiricum Polysaccharides Against Hepatic Carcinoma via Macrophage Phenotype Modulation. International Journal of Biological Macromolecules, 319(Pt 1): Article 145423.

Lu LZ, Huang Z, Guo QQ, et al., 2025, Study on Enhanced Anti-Hepatocellular Carcinoma Effect of Fuzi Polysaccharide Combined with Lenvatinib Through Promoting M1 Polarization of Tumor-Associated Macrophages. China Journal of Chinese Materia Medica, 50(18): 5005–5015.

Yang Y, Rao H, Li Y, et al., 2026, Celastrol Inhibits Intrahepatic Cholangiocarcinogenesis Through Dual Suppression of Glycolysis and Tumor-Associated Macrophages. International Immunopharmacology, 169: Article 116025.

Yang B, Luo J, Wang J, et al., 2025, Liquiritin in Aiduqing Formula Inhibits Breast Cancer Neoangiogenesis by Suppressing CTSK-Mediated Lysosomal Degradation of CXCL1 in Tumor-Associated Macrophages. Phytomedicine, 148: Article 157358.

Jin L, Guo Y, Mao W, et al., 2022, Total Glucosides of Paeony Inhibit Breast Cancer Growth by Inhibiting TAMs Infiltration Through NF-KappaB/CCL2 Signaling. Phytomedicine, 104: Article 154307.

Deng XX, Jiao NN, Hao HF, Xue D, Bai CC, Han SY, 2021, Citri Reticulatae Pericarpium Viride Extract Inhibited Malignant Phenotype of Triple-Negative Breast Cancer Cells in Tumor-Associated Macrophages Microenvironment Through Suppressing IL-10/STAT3/PD-L1 Signaling Pathways. Journal of Ethnopharmacology, 274: Article 114035.

Wang Y, Guo J, Zhou L, et al., 2026, Zuoguiyin Modulates M2 Macrophage Polarization to Inhibit Glycolysis in Esophageal Squamous Cell Carcinoma. Journal of Ethnopharmacology, 362: Article 121404.

Wu J, Zhang XX, Zou X, et al., 2019, The Effect of Jianpi Yangzheng Xiaozheng Decoction and Its Components on Gastric Cancer. Journal of Ethnopharmacology, 235: 56–64.

Yang X, Feng Y, Liu Y, et al., 2021, Fuzheng Jiedu Xiaoji Formulation Inhibits Hepatocellular Carcinoma Progression in Patients by Targeting the AKT/CyclinD1/p21/p27 Pathway. Phytomedicine, 87: Article 153575.

Chen C, Huang R, Wang N, et al., 2024, Fu-Zheng-Yi-Liu Formula Inhibits the Stem Cells and Metastasis of Prostate Cancer via Tumor-Associated Macrophages/C-C Motif Chemokine Ligand 5 Pathway in Tumor Microenvironment. Chinese Journal of Natural Medicines, 22(6): 501–514.

Cheng C, Shou Q, Lang J, et al., 2020, Gehua Jiecheng Decoction Inhibits Diethylnitrosamine-Induced Hepatocellular Carcinoma in Mice by Improving Tumor Immunosuppression Microenvironment. Frontiers in Pharmacology, 11: Article 809.

Wang K, Chen Q, Shao Y, et al., 2021, Anticancer Activities of TCM and Their Active Components Against Tumor Metastasis. Biomedicine & Pharmacotherapy, 133: Article 111044.

Zhang P, Zhang Q, Li S, 2024, Advancing Cancer Prevention Through an AI-Based Integration of Traditional and Western Medicine. Cancer Discovery, 14(11): 2033–2036.

Yu D, Yang P, Lu X, Huang S, Liu L, Fan X, 2023, Single-Cell RNA Sequencing Reveals Enhanced Antitumor Immunity After Combined Application of PD-1 Inhibitor and Shenmai Injection in Non-Small Cell Lung Cancer. Cell Communication and Signaling, 21(1): Article 169.