---
title: "Traditional Chinese Medicine and the Immune Microenvironment in Colorectal Cancer: Mechanisms and"
id: "frontiers-in-immunology-15-traditional-chinese-medicine-remodels-the-immune-microenvironment-of-colorectal"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-15-traditional-chinese-medicine-remodels-the-immune-microenvironment-of-colorectal"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932903"
published_at: "2026-09-03T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Traditional Chinese Medicine and the Immune Microenvironment in Colorectal Cancer: Mechanisms and
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-15-traditional-chinese-medicine-remodels-the-immune-microenvironment-of-colorectal
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932903)
- **Published At:** 2026-09-03T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source referenced is an article titled about how **Traditional Chinese Medicine** (TCM) remodels the **immune microenvironment** of **colorectal cancer**. The original Frontiers in Immunology page header and navigation elements were present in the supplied source, but the article body text was not included. - No experimental data, mechanisms, therapeutic perspectives, study designs, results, or author conclusions were present in the provided source content. Specific molecular targets, immune cell types, clinical outcomes, or TCM formulations were not reported in the supplied text. - Because the source content is missing, no evidence-based summary, mechanisms of action, or clinical recommendations can be extracted or restated from the supplied material. - The supplied material included repeated journal navigation and section listings but lacked substantive article sections (abstract, introduction, methods, results, discussion, conclusions). Therefore, details such as sample sizes, models (in vitro, in vivo, clinical), biomarkers, or adverse events were not available. - Where the article content is absent, readers should consult the original Frontiers in Immunology article page or the published PDF for complete, citable details. This rewrite does not invent or infer any study findings or recommendations absent from the supplied source.
## Clinical Analysis & Structured Key Points
Frontiers | Traditional Chinese medicine remodels the immune microenvironment of colorectal cancer: mechanisms and therapeutic perspectives REVIEW article Front. Immunol. , 03 September 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1932903 Published in Frontiers in Immunology Cancer Immunity and Immunotherapy 7 impact factor 11.3 citescore Editor & Reviewers Edited by J X Junji Xing Reviewed by F G Farid Ghorbaninezhad M A Mohammad A. I. Al-Hatamleh Outline Figures and Tables Figure 1 View in article Figure 2 View in article Table 1 Key mechanisms of TCM-derived isolated compounds and bioactive constituents in modulating the CRC immune microenvironment. View in article Table 2 Key mechanisms of single herbs in modulating the CRC immune microenvironment. View in article Table 3 Key mechanisms of Chinese herbal formulas in modulating the CRC immune microenvironment. View in article Table 4 Key mechanisms of Chinese patent medicines and granule preparations in modulating the CRC immune microenvironment. View in article Table 5 Representative studies of TCM interventions combined with immune checkpoint blockade in CRC. View in article REVIEW article Front. Immunol. , 03 September 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1932903 Traditional Chinese medicine remodels the immune microenvironment of colorectal cancer: mechanisms and therapeutic perspectives Z S Zeanbang Shi 1,2 J M Jie Mei 1,2 Q Z Qinchang Zhang 1,2 L L Liu Li 1,2 H C Haibo Cheng 1,2 * 1. The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China 2. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing, China Article metrics View details Abstract Colorectal cancer (CRC) is a common malignancy of the digestive tract, and its initiation and progression are closely associated with dysregulation of the tumor immune microenvironment. The CRC immune microenvironment consists of effector immune cells, immunosuppressive cells, inflammatory mediators, immune checkpoint pathways, stromal cells, the extracellular matrix, the gut microbiota, and microbial metabolites. Its pathological features include impaired immune recognition and effector immunity, enhanced immunosuppression, extracellular matrix remodeling-mediated immune exclusion, dysregulated inflammatory and immune checkpoint signaling, and disturbances in gut microbiota and metabolism. Traditional Chinese medicine (TCM), characterized by multicomponent, multitarget, and multilevel regulation, has shown potential value in research on the CRC immune microenvironment. Current preclinical studies suggest that TCM-derived isolated compounds and bioactive constituents, single herbs, Chinese herbal formulas, and Chinese patent medicines may improve immune recognition and effector immune function by restoring antigen presentation, promoting dendritic cell maturation and enhancing effector T-cell responses and natural killer cell activity. These interventions may also inhibit immunosuppressive cells, modulate immune checkpoint and inflammation-related signaling, and enhance antitumor immunity by inducing immunogenic forms of tumor cell death. In addition, TCM may alleviate immunosuppression and immune exclusion by modulating stromal remodeling mediated by cancer-associated fibroblasts and regulating the gut microbiota, microbial metabolites, and tumor immunometabolism. In some preclinical models, these effects enhanced the antitumor efficacy of immune checkpoint blockade and provided experimental support for further mechanistic validation and clinical studies of TCM combined with immunotherapy. However, current evidence remains predominantly preclinical, and further clinical validation and assessment of bioavailability, safety, and drug interactions are needed. This review summarizes the composition and pathological features of the CRC immune microenvironment and discusses recent advances in TCM-mediated immune modulation. It also examines current mechanistic evidence and its limitations to inform further mechanistic validation, clinical study design, and translational research. 1 Introduction Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with approximately 1.926 million new cases worldwide and 517, 000 new cases in China in 2022, imposing a substantial disease burden ( 1 , 2 ). The initiation and progression of CRC are driven not only by tumor cell-intrinsic alterations but also by continuous remodeling of the local immune microenvironment. The tumor immune microenvironment is composed of tumor cells, innate and adaptive immune cells, stromal cells, and the cytokines, chemokines, and metabolites released by these cellular components ( 3 ). The extent and spatial distribution of CD3 + and CD8 + T-cell infiltration in tumor tissues are closely associated with recurrence risk and clinical prognosis ( 4 ). During the malignant transformation of colorectal adenomas and subsequent metastatic progression, the composition and functional states of immune cells, as well as the interactions among tumor cells, immune cells, and stromal cells, undergo dynamic changes ( 5 ). Effective antigen presentation, together with the activation of effector T cells and natural killer (NK) cells, contributes to tumor immune clearance. In contrast, the accumulation of immunosuppressive cells, engagement of immune checkpoint pathways, and aberrant inflammatory signaling impair antitumor immunity and influence therapeutic responses across different molecular subtypes of CRC ( 3 ). Accordingly, modulation of the tumor immune microenvironment may help restore antitumor immune responses and alleviate immunosuppression, thereby providing a mechanistic rationale for developing new preventive and therapeutic strategies for CRC. In traditional Chinese medicine (TCM), CRC does not correspond to a specific classical disease entity. According to its clinical manifestations, it is commonly discussed within the categories of “intestinal accumulation” and “intestinal mass.” Although the primary disease site is the intestine, CRC is considered closely related to dysfunction of the spleen and stomach. Its core pathogenesis is characterized by the intermingling of dampness-heat and stasis-toxin, with spleen qi deficiency as the underlying root, thereby forming an accumulation disorder marked by deficiency in origin and excess in manifestation, as well as an intermingling of deficiency and excess. Spleen deficiency impairs the generation of qi and blood and weakens resistance to pathogenic factors, whereas prolonged accumulation of dampness-heat and stasis-toxin may further damage the intestinal tract, resulting in a pathological state of healthy qi deficiency combined with pathogenic excess. From the perspective of modern tumor immunology, healthy qi deficiency may be functionally related to impaired immune surveillance and weakened antitumor effector responses, whereas dampness-heat and stasis-toxin accumulation may be interpreted in association with chronic inflammation, immunosuppression, and intestinal microbial dysbiosis ( 3 ). Therefore, therapeutic strategies based on anticancer detoxification and strengthening healthy qi to consolidate the root can be conceptually linked to the restoration of effector immunity, attenuation of immunosuppression, and improvement of the local tumor microenvironment. TCM is characterized by multiple components, multiple targets, and multilevel regulatory effects, which are compatible with the complexity of the CRC immune microenvironment. Recent studies on TCM-mediated regulation of the CRC immune microenvironment have increasingly extended to immune cells, immune checkpoint pathways, immunometabolism, and gut microecology. Nevertheless, the available evidence remains scattered across diverse therapeutic categories, immune regulatory processes, and mechanistic pathways, and therefore requires systematic integration. Previous reviews have mainly examined the conventional antitumor effects and related signaling pathways of TCM in CRC ( 6 ), the interactions among TCM, the gut microbiota, and CRC ( 7 ), or the potential sensitizing strategies of TCM against barriers to immune checkpoint blockade (ICB) in MSS CRC ( 8 ). These reviews have provided important references for understanding specific mechanisms of action or clinical therapeutic challenges. However, relatively few reviews have used the pathological organization of the CRC immune microenvironment as the central framework. Within such a framework, the effects of different levels of TCM interventions remain insufficiently integrated across immune recognition and effector responses, immunosuppression, stromal remodeling and immune exclusion, inflammatory and immune checkpoint signaling, and gut microbial and metabolic dysregulation. To complement this perspective, the present review integrates evidence on TCM-derived isolated compounds and bioactive constituents, single herbs, Chinese herbal formulas, and Chinese patent medicines. It also critically evaluates the available evidence in relation to disease stage, molecular subtype, model relevance, and translational limitations. Together, these analyses help clarify the potential roles of TCM in CRC prevention, treatment, and immune modulation. 2 Composition and pathological features of the immune microenvironment in colorectal cancer The immune microenvironment of colorectal cancer is not determined by changes in any single immune cell population. Rather, it represents a dynamic network composed of effector immune cells, immunosuppressive cells, inflammatory mediators, immune checkpoint pathways, tumor stroma and extracellular matrix, the gut microbiota, and microbial metabolites. Given the distinct mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and mismatch repair-proficient/microsatellite-stable (pMMR/MSS) molecular subtypes, propensity for liver metastasis, and close involvement of gut microecology in CRC, immune microenvironmental dysregulation in CRC has features that are more specific to intestinal tumor biology. The pathological features of this microenvironment are mainly characterized by impaired antitumor immune responses, enrichment of immunosuppressive components, extracellular matrix remodeling-associated immune exclusion, aberrant inflammatory signaling, dysregulated immune checkpoint pathways, and disturbances in the gut microbiota and microbial metabolism. Together, these alterations constitute the pathological basis of CRC immune microenvironmental dysfunction and influence malignant transformation of colorectal adenomas, primary tumor formation, liver metastasis, and therapeutic response. Therefore, clarifying the composition and abnormal features of the CRC immune microenvironment is essential for understanding how TCM modulates immune states and antitumor responses in CRC. The pathological features of the CRC immune microenvironment are summarized in Figure 1 . Figure 1 Pathological features of the CRC tumor immune microenvironment. Created in BioRender. Shi, Z. (2026) https://BioRender.com/bt65ssy . 2.1 Impaired immune recognition and effector responses In the CRC immune microenvironment, CD3 + T cells and CD8 + T cells serve as key cellular indicators of antitumor immune activity. The level and spatial distribution of CD3 + and CD8 + T-cell infiltration in tumor tissues have been closely associated with patient prognosis, suggesting that effector T cells are important markers for evaluating the local immune status of CRC ( 9 ). However, the presence of effector T-cell infiltration does not necessarily translate into effective tumor killing. CD8 + T cells in CRC exhibit marked heterogeneity, encompassing tumor-reactive cytotoxic populations, bystander T cells, and functionally exhausted cell subsets. These distinct CD8 + T-cell states collectively shape heterogeneous immune microenvironmental profiles ( 10 ). Therefore, impaired effector immunity in CRC cannot be attributed solely to insufficient effector cell abundance, but is also closely associated with limited T-cell antigen specificity, functional exhaustion, and impaired coordination of local antitumor immune responses. Insufficient immune recognition represents an upstream determinant of impaired effector immunity. CD8 + T-cell-mediated tumor killing requires the recognition of tumor antigens, whereas reduced MHC class I (MHC-I)-restricted antigen presentation compromises the ability of CD8 + T cells to recognize and eliminate tumor cells. SOX17-related studies suggest that colorectal adenomas and carcinomas may evade immune surveillance by disrupting IFN-γ-associated immune responses and antigen presentation, indicating that defective antigen presentation may occur across multiple stages of CRC initiation and progression ( 11 ). In parallel, dendritic cells (DCs), particularly subsets with cross-presenting capacity, are essential antigen-presenting cells required for initiating CD8 + T-cell-mediated antitumor responses. Defects in DC abundance or function may therefore restrict antitumor immunity. Notably, in liver metastases from pMMR CRC, the paucity of DCs has been identified as an important factor limiting the efficacy of ICB ( 12 ). Taken together, impaired antigen presentation by tumor cells and insufficient professional antigen-presenting cell support collectively underlie defective immune recognition and constrained effector T-cell responses in CRC. In addition to CD8 + T cells, NK cells are important contributors to local effector immunity in CRC. Unlike CD8 + T cells, NK cells can mediate tumor cell killing independently of classical antigen presentation, primarily through perforin/granzyme-mediated cytotoxicity, and they can produce IFN-γ and other cytokines that support DC and T-cell responses. However, within the tumor microenvironment, hypoxia, lactate accumulation, and inhibitory checkpoint or receptor signals, including programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and natural killer group 2A (NKG2A), may attenuate NK-cell activity, thereby compromising innate effector immunity ( 13 ). In addition, unconventional effector lymphocytes, including γδ T cells, may also contribute to antitumor immunity in CRC. In HLA class I (HLA-I)-deficient tumors, γδ T cells can serve as immunotherapeutic effector cells, providing an alternative mechanism of immune recognition and cytotoxicity for tumors with defective antigen presentation ( 14 ). Tertiary lymphoid structures (TLSs) and B-cell-associated immune responses are also important components of local antitumor immunity in CRC. CCL19 + fibroblasts have been shown to promote TLS formation in CRC liver metastases and enhance antitumor IgG responses ( 15 ). Intratumoral CD8 + CXCR5 + follicular-like cytotoxic T cells are associated with CD19 + CD38 + B cells and TLSs and have prognostic relevance ( 16 ). These findings suggest that TLSs, B cells, and follicular-like cytotoxic T cells function as coordinated components of local effector immunity in CRC. Insufficient formation or functional immaturity of this local immune architecture may therefore compromise antitumor immune responses. 2.2 Enhanced immunosuppression In addition to impaired immune recognition and effector dysfunction, enhanced immunosuppression represents another major feature of the dysregulated immune microenvironment in CRC. Single-cell and spatial omics studies have shown that, during colorectal tumorigenesis, the composition, functional states, and spatial interactions of immune cells undergo continuous remodeling. In this process, myeloid cells, regulatory T cells (Tregs), and stromal cells gradually establish a suppressive niche that favors tumor progression ( 17 ). Among these components, tumor-associated macrophages (TAMs) represent a key myeloid cell population involved in shaping the immunosuppressive microenvironment. Macrophage subsets with distinct spatial distributions and functional states are associated with different prognostic outcomes in patients with CRC, indicating that TAMs do not represent a homogeneous population but instead constitute a highly heterogeneous group of immune regulatory cells ( 18 ). In CRC liver metastases, SPP1 + macrophages can form an immunosuppressive spatial network with fibroblasts, thereby promoting the establishment of a metastatic microenvironment ( 19 ). Liver metastatic disease may also limit the efficacy of immunotherapy through macrophage-mediated T-cell elimination ( 20 ). These findings indicate that TAMs contribute not only to immunosuppression at the primary tumor site but also to immune evasion and therapeutic resistance in metastatic lesions through spatial cellular interactions and the elimination of effector T cells. Myeloid-derived suppressor cells (MDSCs) are major contributors to impaired antitumor immunity. In CRC, MDSCs promote tumor progression by suppressing cytotoxic T lymphocyte activity, reshaping the inflammatory cytokine milieu, and facilitating immune evasion. DCLK1-related studies have shown that tumor cells can recruit MDSCs through the CXCL1-CXCR2 axis, thereby inhibiting tumor-specific cytotoxic T-cell responses ( 21 ). In addition, CXCR2 + MDSCs have been implicated in promoting colitis-associated tumorigenesis ( 22 ). These findings suggest that, during inflammation-associated colorectal tumorigenesis, MDSCs are not merely bystander immune infiltrates but constitute an important cellular link connecting chronic inflammation, immunosuppression, and tumor formation. In addition to TAMs and MDSCs, Tregs, tumor-associated neutrophils (TANs), and cancer-associated fibroblasts (CAFs) also participate in the establishment of an immunosuppressive network. Spatial and single-cell colocalization analyses have shown that midkine (MDK)-related signaling can shape a Treg-associated immunosuppressive niche, suggesting that the function of Tregs is not limited to the secretion of inhibitory mediators such as IL-10 and transforming growth factor-β (TGF-β), but is also closely linked to their spatial localization and cellular interactions ( 23 ). TANs may undergo tissue-specific reprogramming into pro-angiogenic neutrophil states, thereby contributing to CRC vascularization and microenvironmental remodeling ( 24 ). In parallel, IL1R1 + CAFs have been shown to drive tumor progression and immunosuppression, indicating that stromal cells are not merely passive scaffolds but active participants in immune exclusion and the formation of an immunosuppressive microenvironment ( 25 ). Overall, enhanced immunosuppression in CRC is not driven by any single cell type alone. Rather, it results from spatially coordinated interactions among multiple cellular populations, including TAMs, MDSCs, Tregs, TANs, and CAFs, which collectively constrain effector immune responses and promote tumor progression. 2.3 Extracellular matrix remodeling and immune exclusion The extracellular matrix (ECM) is a major structural component of the CRC tumor stroma and an important factor influencing immune cell infiltration and immunotherapeutic response. Studies on immuno-collagenic subtypes have shown that collagen deposition and immune infiltration jointly predict tumor responses to ICB. Tumors characterized by high collagen deposition and low immune infiltration are generally associated with poor responsiveness to immunotherapy ( 26 ). This evidence indicates that ECM and collagen-related structural features are not merely stromal alterations, but may also serve as important parameters for evaluating immune exclusion and immunotherapeutic response ( 27 ). Spatial omics and single-cell transcriptomic analyses in CRC patients further showed that the boundary between tumor and stroma differs in spatial
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