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Increasing evidence indicates that metabolic enzymes function not only as bioenergetic regulators but also as active modulators of immune signaling, immune cell fate, and immune checkpoint expression. To elucidate these complex immunometabolic networks, this review utilizes fructose\u20101,6\u2010bisphosphatase 1 (FBP1)\u2014a key gluconeogenic enzyme\u2014as a paradigmatic metabolic gatekeeper to illustrate how metabolic dysregulation drives tumor progression. By examining both the canonical metabolic effects and noncanonical signaling mechanisms of such enzymes, we synthesize recent advances demonstrating how metabolic rewiring promotes glycolytic reprogramming, immune suppression, and resistance to immunotherapy. Specifically, we explore broad mechanisms of immune evasion, including STAT3\u2013PD\u2010L1 regulation, modulation of innate immune surveillance, T cell exhaustion, and remodeling of stromal and fibrotic tumor niches. Furthermore, we discuss emerging therapeutic strategies targeting these immunometabolic pathways, encompassing small\u2010molecule modulators, vitamin\u2010 and gene\u2010based interventions, nanotechnology\u2010enabled delivery systems, and metabolism\u2010informed combination immunotherapy. Finally, we highlight key challenges, including metabolic heterogeneity and context\u2010dependent enzyme function, emphasizing the need for biomarker\u2010guided precision strategies to translate fundamental immunometabolic insights into durable and safe cancer therapies.<\/jats:p>","DOI":"10.1002\/mco2.70801","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T07:23:33Z","timestamp":1780903413000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Regulation of Immune Responses: Molecular Mechanisms, Diseases, and Therapeutic Targets"],"prefix":"10.1002","volume":"7","author":[{"given":"Chunwei","family":"Li","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"},{"name":"Department of Pharmacology Henan Provincial People's Hospital  Zhengzhou 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