Tumor Immune Regulation by Natural Products: Mechanistic Insights and Therapeutic Potential

Frequently evolving into a highly immunosuppressive niche that facilitates tumor growth and metastasis, the tumor microenvironment (TME) serves as the primary site for interactions between tumor cells and the host immune system. Reversing this immunosuppressive state therefore represents a pivotal strategy for antitumor therapy. Natural products possess the distinct advantages of multi-targeted and multi-pathway mechanisms, as well as the capacity to enhance therapeutic efficacy while attenuating systemic toxicity. These characteristics perfectly align with the core principles of antitumor immunotherapy. Accumulating evidence demonstrates that natural products including Ganoderma lucidum polysaccharides, Astragalus polysaccharides, and Lycium barbarum polysaccharides, as well as bioactive single compounds such as curcumin, resveratrol, and bufalin, exert potent antitumor immunotherapeutic effects by remodeling the suppressive TME. Consequently, they are increasingly being utilized as synergists or adjuvants in advanced therapeutic modalities, which include adoptive immune cell therapy, cancer vaccines, and immune checkpoint inhibitors. In addition, the discovery of novel potential regulatory factors for tumor immunotherapy from natural products has attracted significant attention. This review provides a comprehensive overview of the latest progress on how natural products reshape the immunosuppressive landscape and enhance the systemic antitumor response. Ultimately, this review both underscores the immense translational potential of natural products in tumor immunotherapy and highlights critical directions for future standardized research.