Journal of Immunology Research · Published 2026-01-01 · DOI 10.1155/jimr/1138548
Metal ions are key regulators of the neuro–immune–tumor axis. Recent studies provide concrete evidence that neuronal Ca2+ pulses drive tumor–neuron integration and shape immune signaling. Synaptic Zn2+ and ZIP transporters modulate synaptic transmission and tumor growth. Tumor iron accumulation fuels proliferation while creating a clear ferroptosis vulnerability. Copper promotes angiogenesis, lysyl oxidase (LOX)-mediated extracellular matrix (ECM) remodeling and metastasis, and implicates cuproptosis as a therapeutic target. Mn potentiates cyclic GMP-AMP synthase (cGAS)–STING signaling and serves as both an immune adjuvant and manganese-enhanced magnetic resonance imaging (MEMRI) contrast. Besides, Mg and K+ regulate kinase/T-cell receptor (TCR) function and tumor–neuron excitability, respectively. Despite these advances, major gaps persist, notably limited spatial and temporal mapping of labile metal pools, a paucity of cell-type-specific causal perturbations, and underdeveloped tumor-targeted metal-modulating therapies with proven safety. We therefore propose a focused research agenda: integrate spatial metallomics with single-cell multiomics, deploy metal-sensitive longitudinal imaging, apply conditional genetic and chemogenetic perturbations and organotypic models to dissect neuro–immune cross-talk, and implement preclinical pipelines emphasizing tumor-selective delivery and comprehensive safety testing.
Abstract from DOAJ. Public domain (CC0 1.0).
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