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Updated: Sep 12, 2026

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
The emerging cellular metal ions-immune axis in cancer
Sha Qin1, Minmin Xiang2, Tania Tao3
1Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Pathology, Xiangya School of Basic Medical Science, Central South University, Changsha, Hunan, China.
Abstract:
Cancer immunotherapy is frequently hindered by the immunosuppressive tumor microenvironment. Although metal ions have been viewed as essential nutrients or cytotoxic payloads, emerging evidence reveals that they are potent immune modulators that orchestrate the cancer-immunity cycle. Here, we synthesize how ionic competition dictates immune cell plasticity and metabolic fate. We detail how metal ions regulate cell death pathways and immune signaling cascades, including the cyclic GMP-AMP synthase-stimulator of interferon genes and nuclear factor kappa B pathways, as well as immunological synapse formation and immune cell responses. Finally, we evaluate the clinical potential of targeting the metal ions-immune axis, from metallomic biomarkers, including Zrt-/Irt-like protein transporters and ion channels, to metallo-immunotherapy strategies. This framework provides a mechanistic roadmap for developing combination therapies to overcome immunotherapy resistance and harness the cellular metallome for precision oncology.
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