Multidimensional Regulation of Metal Ions in the Tumor Microenvironment and Innovative Strategies for Diagnosis and Therapy.

Metal ions serve as key regulators of the dynamic equilibrium within the tumor microenvironment (TME). In recent years, the TME has emerged as a central regulatory hub for tumor initiation, progression, and metastasis; its complexity has become both a frontier and a major challenge in oncology research. Current therapies are often constrained by immune tolerance, metabolic heterogeneity, and microenvironment-mediated escape mechanisms, necessitating breakthroughs in novel targets and strategies. Metal ions, functioning as enzyme cofactors, signaling molecules, and redox regulators, profoundly affect tumor progression by modulating redox homeostasis, immune responses, and metabolic reprogramming. This review provides a comprehensive overview of recent advances in metal ion-mediated regulation of the TME. It focuses on elucidating the multidimensional mechanisms by which metal ions facilitate immunogenic remodeling and metabolic interactions, and prospectively explores innovative metal-ion-based diagnostic and therapeutic strategies. It further highlights the potential of personalized metal metabolomics to advance precision oncology and facilitate the clinical translation of metal ion-based theranostic strategies.