Home›Oncology› Traditional Chinese medicine may modulate immune resistance barriers in microsatellite-stable colorectal cancer
Traditional Chinese medicine may modulate immune resistance barriers in microsatellite-stable colorectal cancerTraditional Chinese medicine may help some patients with colorectal cancer
Frontiers in MedicinePublished July 3, 2026Study authors: Dawei Wang, Yawei Wang, Xuan WangDOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
Note that while TCM may modulate immune barriers in MSS-CRC, clinical evidence remains limited and indirect.
This narrative review examines the potential of various traditional Chinese medicine (TCM) components, including specific herbal formulas and electroacupuncture, to address immune-resistance mechanisms in microsatellite-stable colorectal cancer (MSS-CRC). The authors synthesize findings regarding how TCM may modulate barriers such as low tumor immunogenicity, impaired antigen presentation, and myeloid- or Treg-dominated immunosuppression.
The review highlights several potential pathways for action, including immunometabolic remodeling, dendritic-cell mitophagy, microbiota-driven tumor microenvironment remodeling, and STING-dependent immune activation. These mechanisms are hypothesized to potentially improve the efficacy of current treatments in this specific molecularly defined population.
However, the authors emphasize that direct formula-specific clinical evidence for immunotherapy sensitization in MSS-CRC is currently limited. Most available data regarding herbal formulas remain preclinical or indirect. Consequently, while TCM represents a potential candidate strategy for sensitizing patients to immunotherapy, it is not an established standard combination approach. The certainty of these findings is low due to the lack of large-scale, formula-specific clinical trials in molecularly defined MSS-CRC populations.
How this fits prior evidence
This narrative review addresses a gap in current management strategies for microsatellite-stable colorectal cancer by exploring non-traditional interventions. While nanomedicine delivery systems are considered as a theoretical strategy to enhance immunotherapy in colorectal cancer, this review explores TCM as another potential but less established method for overcoming immune resistance.
For many people living with microsatellite-stable colorectal cancer (MSS-CRC), standard treatments can be difficult because the cancer is often resistant to certain therapies. This makes finding new ways to jumpstart the immune system a high priority for patients and doctors alike.
Researchers looked into how traditional Chinese medicine (TCM) might change the way the body responds to treatment. They found that specific herbal formulas could potentially break down barriers that keep the cancer hidden from the immune system. This includes improving how the body recognizes cancer cells and changing the environment around the tumor.
While these findings are promising, it is important to know that most of this evidence comes from early studies rather than large human trials. Because direct clinical evidence for specific herbal formulas in this type of cancer is currently limited, TCM is not yet an established standard treatment. It remains a potential strategy that may need more research before it can be used as a routine combination therapy.
What this means for you:
Traditional Chinese medicine may help overcome immune resistance in certain colorectal cancers, but more clinical trials are needed.
Common questions
What is the role of traditional Chinese medicine in this type of cancer?
Traditional Chinese medicine (TCM) may act as a way to help the body overcome resistance. It could potentially improve how the immune system recognizes and attacks tumors by changing the environment around the cancer cells.
Is this treatment currently standard for colorectal cancer?
No, traditional Chinese medicine is not yet an established standard combination approach for this type of cancer. Most evidence for these herbal formulas is still indirect or based on early research rather than large-scale clinical trials.
How much evidence is there for these specific herbal formulas?
Direct clinical evidence specifically for these herbal formulas in patients with microsatellite-stable colorectal cancer is currently limited. Most of the data comes from preclinical studies rather than direct human trials.
Microsatellite-stable colorectal cancer (MSS-CRC) is refractory to immune checkpoint inhibitors (ICIs), mainly because of low tumor immunogenicity, impaired antigen presentation, immune exclusion, and myeloid- or Treg-dominated immunosuppression. Traditional Chinese medicine (TCM), characterized by multi-component and multi-target regulation, may provide complementary approaches for modulating these resistance barriers. This review summarizes the rationale, evidence, and translational requirements for integrating TCM with ICI-based therapy in MSS-CRC.
To evaluate the potential of TCM to regulate immune-resistance mechanisms in MSS-CRC and to propose a barrier-oriented framework for rational TCM–ICI combination strategies.
A structured narrative review was conducted in PubMed, Web of Science, Embase, Scopus, CNKI, and Wanfang for studies published from January 2019 to March 2026. Searches covered MSS/pMMR CRC, immune checkpoint blockade, TCM interventions, tumor microenvironment, microbiota, immunometabolism, syndrome patterns, active constituents, and herbal quality control. Eligible studies addressed MSS/pMMR CRC immunotherapy, TCM or phytomedicine-based interventions, or immune-resistance mechanisms. Direct MSS/pMMR CRC studies involving ICI combinations were prioritized, while broader CRC, cross-cancer, pharmacological, and computational studies were used as supportive evidence.
Selected TCM interventions may improve ICI responsiveness in MSS-CRC when matched to specific resistance barriers. Representative interventions include Zhenqi Fuzheng Granules, Shenqi Yichang Formula, Gegen Qinlian Decoction, modified Shenling Baizhu San, Changweiqing, and electroacupuncture-related evidence. These interventions have been linked to immunometabolic remodeling, dendritic-cell mitophagy and antigen presentation, microbiota-driven TME remodeling, Tfh–B-cell interactions, and STING-dependent immune activation. However, direct formula-specific clinical evidence for ICI sensitization in molecularly defined MSS-CRC remains limited. Clinical-translational evidence includes an early phase II study of electroacupuncture combined with fruquintinib and sintilimab in refractory MSS-mCRC, whereas most herbal-formula evidence remains preclinical or indirect. We therefore propose matching TCM interventions and active ingredients to dominant immune-resistance phenotypes and integrating syndrome-informed host-state stratification. These hypotheses require validation using causal assays, organoid-immune co-culture, single-cell/spatial omics, pharmacological standardization, and biomarker-enriched clinical trials.
TCM may serve as a complementary, mechanism-informed candidate sensitization strategy for MSS-CRC immunotherapy, but it is not an established standard combination approach. Future translation requires formula-specific and component-level validation, reproducible immune and microbiota-metabolic biomarkers, TCM syndrome assessment, herbal quality control, safety monitoring, and clinically meaningful outcomes.
