Dynamic remodeling of the tumor immune microenvironment: immunometabolic regulatory networks of astragalus polysaccharides and astragaloside IV

Abstract

The highly heterogeneous tumor immune microenvironment (TIME) remains a major obstacle to effective cancer immunotherapy. This review systematically elucidates the immunometabolic regulatory networks of the primary active constituents of Astragalus membranaceus—Astragalus polysaccharides (APS) and Astragaloside IV (AS-IV)—within the TIME. Synthesizing preclinical evidence up to January 2026, we focus on immune cell modulation, metabolic interventions, and advanced translational strategies. Evidence indicates that APS and AS-IV modulate the TIME through two primary mechanisms: regulating cellular immunity (APS facilitates dendritic cell maturation and attenuates T-cell exhaustion, while AS-IV promotes an immunostimulatory M1 macrophage polarization) and modulating tumor bioenergetics (inhibiting aerobic glycolysis and lipid metabolism to alleviate resource competition). Furthermore, experimental models demonstrate that co-delivering these agents via advanced nanoplatforms or in combination with immune checkpoint inhibitors significantly enhances anti-tumor responses. Ultimately, APS and AS-IV exhibit promising potential to shift the TIME from an immunosuppressive state toward an immunostimulatory microenvironment, highlighting their potential transition from empirical adjuvants to rationally designed precision immunotherapies.