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<p>Dendritic cells (DCs) are key initiators of antitumor immunity, yet the metabolic drivers governing their activation remain incompletely defined. Here, we show that the fungal immunomodulator β-glucan induces robust immune-metabolic reprogramming in bone marrow-derived DCs (BMDCs), characterized by coordinated increases in glycolysis and tricarboxylic acid cycle activity. This metabolic shift is essential for BMDCs activation, as inhibition of glycolysis or oxidative metabolism diminishes β-glucan-induced costimulatory molecule expression, proinflammatory cytokine production and T-cell priming. Multi-omics profiling identifies enolase 3 (ENO3) as a key glycolytic regulator selectively upregulated by β-glucan. ENO3 knockdown reduces glycolytic flux, decreases mitochondrial ATP and ROS production, and consequently impairs BMDCs maturation and CD8⁺ T-cell responses. In DC-specific ENO3-knockout mice, ENO3 deficiency significantly compromises the antitumor efficacy of β-glucan, which characterized by accelerated tumor growth, impaired DCs activation, reduced CD8⁺ T-cell infiltration, and an immunosuppressive tumor milieu. These findings reveal ENO3 as a critical metabolic regulator linking β-glucan sensing to DC-mediated antitumor immunity.</p>

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ENO3-mediated glycolytic reprogramming participates in β-glucan-induced dendritic cells activation and anti-tumor responses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月16日

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  • Jun Ding,
  • Yongzhe Hao,
  • Meng Yuan,
  • Jie Pan,
  • Yewen Xie,
  • Xiao Sun,
  • Yongling Ning,
  • Chunjian Qi

摘要

Dendritic cells (DCs) are key initiators of antitumor immunity, yet the metabolic drivers governing their activation remain incompletely defined. Here, we show that the fungal immunomodulator β-glucan induces robust immune-metabolic reprogramming in bone marrow-derived DCs (BMDCs), characterized by coordinated increases in glycolysis and tricarboxylic acid cycle activity. This metabolic shift is essential for BMDCs activation, as inhibition of glycolysis or oxidative metabolism diminishes β-glucan-induced costimulatory molecule expression, proinflammatory cytokine production and T-cell priming. Multi-omics profiling identifies enolase 3 (ENO3) as a key glycolytic regulator selectively upregulated by β-glucan. ENO3 knockdown reduces glycolytic flux, decreases mitochondrial ATP and ROS production, and consequently impairs BMDCs maturation and CD8⁺ T-cell responses. In DC-specific ENO3-knockout mice, ENO3 deficiency significantly compromises the antitumor efficacy of β-glucan, which characterized by accelerated tumor growth, impaired DCs activation, reduced CD8⁺ T-cell infiltration, and an immunosuppressive tumor milieu. These findings reveal ENO3 as a critical metabolic regulator linking β-glucan sensing to DC-mediated antitumor immunity.