Scholarlink

<p>Low-dose radiotherapy (LDRT) has emerged as a promising immunomodulatory strategy by activating the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, thereby reprogramming the tumor immune microenvironment (TIME). LDRT induces DNA damage and cytosolic dsDNA accumulation, leading to cGAS-STING activation and subsequent production of type I interferon and proinflammatory cytokines. Consequently, LDRT promotes dendritic cell maturation, enhances CD8⁺ T cell infiltration and cytotoxicity, repolarizes macrophages toward an anti-tumor, immunostimulatory phenotype, and suppresses myeloid-derived suppressor cells and regulatory T cells (Tregs). However, sustained cGAS–STING activation may paradoxically induce immunosuppression through PD-L1 upregulation, T cell exhaustion, and enrichment of inhibitory cells. Combining LDRT with immune checkpoint inhibitors, STING agonists, chemotherapy, or CAR-T cell therapy synergistically amplifies antitumor immunity by overcoming TIME suppression and fostering long-term immune memory. Challenges such as radiotherapy heterogeneity, dose optimization, and STING pathway mutations require precise strategies including image-guided radiotherapy, nanocarrier-based delivery, and biomarker-driven patient stratification. This review highlights the dual role of LDRT-mediated cGAS–STING signaling in TIME remodeling and provides a foundation for developing novel combinatorial immunotherapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Low-dose radiotherapy remodels the tumor immune microenvironment via the cGAS–STING pathway: mechanisms, challenges, and combination therapy strategies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月10日

查看全文
  • Yongze He,
  • Xianhu Zeng,
  • Qianyi Liu,
  • Linsen Zhou,
  • Ying Tang,
  • Shuotong Liu,
  • Xiaobin Wang,
  • Shiyan Shen,
  • Jialin Ji,
  • Zhen Liu,
  • Jiangping Li

摘要

Low-dose radiotherapy (LDRT) has emerged as a promising immunomodulatory strategy by activating the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, thereby reprogramming the tumor immune microenvironment (TIME). LDRT induces DNA damage and cytosolic dsDNA accumulation, leading to cGAS-STING activation and subsequent production of type I interferon and proinflammatory cytokines. Consequently, LDRT promotes dendritic cell maturation, enhances CD8⁺ T cell infiltration and cytotoxicity, repolarizes macrophages toward an anti-tumor, immunostimulatory phenotype, and suppresses myeloid-derived suppressor cells and regulatory T cells (Tregs). However, sustained cGAS–STING activation may paradoxically induce immunosuppression through PD-L1 upregulation, T cell exhaustion, and enrichment of inhibitory cells. Combining LDRT with immune checkpoint inhibitors, STING agonists, chemotherapy, or CAR-T cell therapy synergistically amplifies antitumor immunity by overcoming TIME suppression and fostering long-term immune memory. Challenges such as radiotherapy heterogeneity, dose optimization, and STING pathway mutations require precise strategies including image-guided radiotherapy, nanocarrier-based delivery, and biomarker-driven patient stratification. This review highlights the dual role of LDRT-mediated cGAS–STING signaling in TIME remodeling and provides a foundation for developing novel combinatorial immunotherapies.