Traditional Chinese medicine remodels the immune microenvironment of colorectal cancer: mechanisms and therapeutic perspectives.

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.