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Background <p>Zinc finger proteins (ZFPs) represent the largest and most structurally diverse family of transcription factors in the human genome. They function through characteristic zinc finger domains that enable specific binding to DNA, RNA, and proteins, playing a central regulatory role in the tumor immune microenvironment.</p> Main body <p>This review systematically examines the dual functions of ZFPs in dynamically regulating both innate and adaptive immune responses in cancer. At the innate immunity level, ZFPs precisely control dendritic cell (DC) fate determination, dictate macrophage polarization, balance natural killer (NK) cell activation, mediate myeloid-derived suppressor cell (MDSC) immunosuppressive function, and modulate innate immune sensors and inflammasomes. Within adaptive immunity, ZFPs critically influence T cell effector function and regulate B cell differentiation. Building on these, diverse immunotherapeutic strategies targeting ZFPs are now emerging. These include gene-editing, small molecules and proteolysis-targeting chimeras (PROTACs), synergistic combinations with immune checkpoint blockade, and ZFP-engineered chimeric antigen receptor T (CAR-T) cells.</p> Conclusions <p>As pivotal nodes within the tumor immune regulatory network, ZFP-targeting strategies offer novel opportunities to overcome current therapeutic bottlenecks.</p>

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Rewiring tumor immunity via zinc finger proteins: a new frontier in cancer immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月11日

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  • Zimu Zhou,
  • Le Wu,
  • Jun-Li Luo,
  • Zhijun Li,
  • Shangwei Zhong

摘要

Background

Zinc finger proteins (ZFPs) represent the largest and most structurally diverse family of transcription factors in the human genome. They function through characteristic zinc finger domains that enable specific binding to DNA, RNA, and proteins, playing a central regulatory role in the tumor immune microenvironment.

Main body

This review systematically examines the dual functions of ZFPs in dynamically regulating both innate and adaptive immune responses in cancer. At the innate immunity level, ZFPs precisely control dendritic cell (DC) fate determination, dictate macrophage polarization, balance natural killer (NK) cell activation, mediate myeloid-derived suppressor cell (MDSC) immunosuppressive function, and modulate innate immune sensors and inflammasomes. Within adaptive immunity, ZFPs critically influence T cell effector function and regulate B cell differentiation. Building on these, diverse immunotherapeutic strategies targeting ZFPs are now emerging. These include gene-editing, small molecules and proteolysis-targeting chimeras (PROTACs), synergistic combinations with immune checkpoint blockade, and ZFP-engineered chimeric antigen receptor T (CAR-T) cells.

Conclusions

As pivotal nodes within the tumor immune regulatory network, ZFP-targeting strategies offer novel opportunities to overcome current therapeutic bottlenecks.