Home›Infectious Disease› Traditional Chinese Medicine may reprogram tumor-associated macrophages to overcome chemotherapy resistance in gastric cancer
Traditional Chinese Medicine may reprogram tumor-associated macrophages to overcome chemotherapy resistance in gastric cancerTraditional Chinese Medicine may help fight gastric cancer cells
Frontiers in MedicinePublished August 21, 2026Study authors: Xiaodong Zhuang, Qiang Yang, Liangjiu Huang, Risheng Liu, Ting Ma, Liwen Guan, Yana ZhengDOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Note that TCM-mediated reprogramming of tumor-associated macrophages may offer a potential strategy to overcome chemoresistance.
This narrative review synthesizes current research on the role of Traditional Chinese Medicine (TCM) in modulating the tumor microenvironment in gastric cancer. The authors focus specifically on how TAMs promote progression through pathways such as FOXQ1/EMT and exosomal ApoE/PI3K/AKT, while contributing to resistance against standard chemotherapies including 5-fluorouracil, cisplatin, and oxaliplatin.
The review highlights that specific TCM formulae, such as Yi-qi-hua-yu-jie-du decoction and Jianpi Yangzheng formula, may reprogram TAMs by modulating the PP2A/PI3K/AKT/NF-kB signaling pathway. Additionally, active monomers including Actinidia eriantha polysaccharide and Dendrobium officinale polysaccharide are reported to promote M1-like macrophage polarization and reverse M2-like macrophage-mediated immunosuppression.
A primary limitation of this review is that it summarizes mechanistic evidence rather than providing clinical trial data for human patients. While the findings suggest TCM-mediated TAM reprogramming is a promising adjunctive strategy to improve chemotherapy and immunotherapy outcomes, the lack of large-scale human trials means these results should be interpreted with caution in clinical practice.
How this fits prior evidence
This narrative review addresses a gap in understanding how the tumor microenvironment contributes to chemotherapy resistance. While prior coverage established that pembrolizumab plus chemotherapy improves outcomes in HER2-negative advanced gastric cancer, this review explores an alternative mechanism for improving treatment efficacy by targeting TAMs via TCM components.
Gastric cancer is a tough battle because the body's own immune system can sometimes be tricked into helping the tumor grow. Specifically, certain immune cells called TAMs act as helpers for the cancer, allowing it to spread and resist standard treatments like 5-fluorouracil or cisplatin.
Researchers are looking at how Traditional Chinese Medicine (TCM) might change this dynamic. The review highlights specific herbal formulas and active compounds that may reprogram these stubborn immune cells. By shifting them into a state that fights the cancer rather than supporting it, these treatments could potentially make chemotherapy and immunotherapy more effective.
It is important to note that while these findings are promising for future treatments, this was a narrative review of existing research. This means the results are based on gathered evidence rather than new clinical trials in human patients. Talk with your doctor about how these options might fit into a specific treatment plan.
What this means for you:
Traditional Chinese Medicine may help reprogram immune cells to better fight gastric cancer and resist chemotherapy.
Common questions
What is the role of TAMs in gastric cancer?
TAMs are a type of immune cell that can actually help gastric cancer grow. They promote the spread of the cancer, help it create new blood vessels, and make it harder for standard chemotherapy drugs like 5-fluorouracil, cisplatin, and oxaliplatin to work effectively.
How does Traditional Chinese Medicine work against these cells?
Specific herbal formulas, such as Yi-qi-hua-yu-jie-du decoction and Jianpi Yangzheng formula, may reprogram TAMs. They do this by changing the signaling pathways within the cells to reduce the immune system's help to the tumor.
Are these herbal treatments proven for human patients?
The current evidence comes from a narrative review of research, not from direct clinical trials in humans. While these findings show promise as an extra way to boost chemotherapy, you should always consult your doctor regarding specific treatment options.
Gastric cancer (GC) remains a leading cause of cancer-related mortality, with progression driven largely by the tumor microenvironment (TME). Tumor-associated macrophages (TAMs), the most abundant immune cells in the GC stroma, drive immune evasion, angiogenesis, metastasis, and chemoresistance through polarization toward an M2-like phenotype.
This review aims to systematically consolidate the multifaceted molecular mechanisms by which TAMs promote GC aggressiveness and therapeutic resistance, and to categorize the current experimental evidence regarding Traditional Chinese Medicine (TCM) interventions that target TAM reprogramming for anti-GC therapy.
This narrative review summarizes current evidence retrieved from PubMed, Web of Science, Embase, Scopus, the Cochrane Library, CNKI, Wanfang Data, and the VIP Database from database inception to May 2026, with no language restrictions. The search strategy combined terms related to “gastric cancer” (e.g., gastric cancer, stomach cancer, gastric carcinoma), “tumor-associated macrophages” (e.g., tumor-associated macrophages, TAMs, macrophage polarization, M1 macrophages, M2 macrophages), and “Traditional Chinese Medicine” (e.g., traditional Chinese medicine, Chinese herbal medicine, herbal formula, natural product, active monomer, polysaccharide, terpenoid, alkaloid, catechin), using Boolean operators (AND, OR). Additional relevant studies were identified by manual screening of reference lists of included articles and relevant reviews. Studies were included if they investigated the biological roles of TAMs within the GC TME or the molecular mechanisms by which TCM modulates TAMs, covering both classical herbal formulae and bioactive monomers.
Mechanistically, TAMs promote GC cell proliferation, invasion, and metastasis through the FOXQ1/EMT axis and exosomal ApoE/PI3K/AKT signaling pathways; promote angiogenesis through the VEGF/NF-κB and COX-2/MMP9 signaling pathways; induce resistance to 5-fluorouracil, cisplatin, and oxaliplatin via exosomal miR-21/PTEN, miR-1911-5p, and circ0008253; and mediate immune evasion through the PD-L1- and CLEVER-1-mediated immune checkpoint pathways. Therapeutically, TCM formulae, including Yi-qi-hua-yu-jie-du decoction and Jianpi Yangzheng formula, effectively reprogram TAMs by modulating the PP2A/PI3K/AKT/NF-κB signaling pathway and the exosomal miR-513b-5p/PTEN axis. Active monomers, including Actinidia eriantha polysaccharide, Dendrobium officinale polysaccharide, sophoridine, and epigallocatechin gallate, promote M1-like macrophage polarization and reverse M2-like macrophage-mediated immunosuppression through the PD-1/PD-L1, STAT6/PPAR-γ/JAGGED1/NOTCH1, and TLR4/IRF3 signaling pathways.
TCM-mediated TAM reprogramming represents a promising adjunctive strategy to enhance chemotherapy and immunotherapy efficacy in GC.
