{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:46:29Z","timestamp":1787755589986,"version":"build-2784847793"},"reference-count":179,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>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\u2014Astragalus polysaccharides (APS) and Astragaloside IV (AS-IV)\u2014within 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.<\/jats:p>","DOI":"10.3389\/fphar.2026.1833078","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:45:22Z","timestamp":1787751922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic remodeling of the tumor immune microenvironment: immunometabolic regulatory networks of astragalus polysaccharides and astragaloside IV"],"prefix":"10.3389","volume":"17","author":[{"given":"Ziming","family":"Xu","sequence":"first","affiliation":[{"name":"First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Digital Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]},{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Digital Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]},{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Qi","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Digital Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]},{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/imm.12941","article-title":"The opposing roles of CD4+ T cells in anti-tumour immunity","volume":"154","author":"Ahrends","year":"2018","journal-title":"Immunology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.lfs.2015.01.026","article-title":"Sulforaphane induces ROS mediated induction of NKG2D ligands in human cancer cell lines and enhances susceptibility to NK cell mediated lysis","volume":"126","author":"Amin","year":"2015","journal-title":"Life Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.ijbiomac.2022.11.048","article-title":"Polysaccharides from astragalus membranaceus elicit T cell immunity by activation of human peripheral blood dendritic cells","volume":"223","author":"An","year":"2022","journal-title":"Int. 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