Ginsenosides as Emerging Adjuvants for Immunotherapy in Gastrointestinal Cancers.

Gastrointestinal (GI) cancers remain a leading cause of cancer-related death worldwide, and many patients with advanced disease still respond poorly to standard treatments such as surgery, chemotherapy, and radiotherapy. Immune checkpoint inhibitors have changed the management of several solid tumors, but their benefit in most GI malignancies is limited by low tumor mutational burden, microsatellite stability, and "cold" tumor immune microenvironments. This has created interest in safe adjuvant agents that can boost antitumor immunity and improve responses to immunotherapy. Ginseng, a traditional medicinal herb, contains ginsenosides and polysaccharides with documented antitumor and immunomodulatory activities. Experimental studies in liver, colorectal, gastric, and esophageal cancer models show that selected ginsenosides can promote apoptosis, modulate DNA damage responses, inhibit angiogenesis, reshape inflammatory signaling, and downregulate PD-L1 or other resistance pathways. Ginseng-derived nanoparticles and liposomal formulations further suggest a role in drug delivery and microenvironment remodeling. At the same time, clinical experience from traditional Chinese medicine indicates that ginseng-based preparations may alleviate cancer-related fatigue, support host immunity, and enhance tolerance to chemoradiotherapy. However, the pharmacological targets, optimal combinations, and predictive biomarkers for ginsenoside-based adjuvant therapy remain poorly defined. Integration of systems pharmacology, single-cell technologies, and modern clinical trial design will be essential to clarify the role of ginsenosides as partners in immunotherapy for GI cancers.