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<p>Glioblastoma (GBM) presents a significant challenge because of its immunosuppressive microenvironment. The standard treatment protocol, including surgery, radiotherapy, and temozolomide, has been unable to alleviate immunosuppression. Doxorubicin chemotherapy induces immunogenic cell death in cancer cells, reshaping an immune-activated microenvironment. Here, we investigated the mechanism of immune activation induced by doxorubicin in tumor-associated macrophages (TAMs). Radiotherapy and temozolomide plus doxorubicin inhibited tumor growth and reduced the levels of immunosuppressive markers. Mechanically, doxorubicin promotes the production of lactate through activating lactate dehydrogenase A (LDHA) to upregulate the transcription of inflammatory cytokines. Our study confirmed a new mechanism by which doxorubicin remodels the tumor microenvironment by promoting the glycolytic process and lactic acid production, suggesting that combining radiotherapy and temozolomide with doxorubicin chemotherapy may be a potential strategy for GBM treatment.</p><p></p>

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Doxorubicin promotes the production of inflammatory cytokines in tumor-associated macrophages through activating lactate dehydrogenase A

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月31日

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  • Bin Liu,
  • Wei Yang,
  • Shuo Feng,
  • Xingning Jiang,
  • Jingfan Lu,
  • Fei Wang,
  • Yaowen Hu,
  • Yanhao Liu,
  • Haifeng Ma,
  • Ting Sun

摘要

Glioblastoma (GBM) presents a significant challenge because of its immunosuppressive microenvironment. The standard treatment protocol, including surgery, radiotherapy, and temozolomide, has been unable to alleviate immunosuppression. Doxorubicin chemotherapy induces immunogenic cell death in cancer cells, reshaping an immune-activated microenvironment. Here, we investigated the mechanism of immune activation induced by doxorubicin in tumor-associated macrophages (TAMs). Radiotherapy and temozolomide plus doxorubicin inhibited tumor growth and reduced the levels of immunosuppressive markers. Mechanically, doxorubicin promotes the production of lactate through activating lactate dehydrogenase A (LDHA) to upregulate the transcription of inflammatory cytokines. Our study confirmed a new mechanism by which doxorubicin remodels the tumor microenvironment by promoting the glycolytic process and lactic acid production, suggesting that combining radiotherapy and temozolomide with doxorubicin chemotherapy may be a potential strategy for GBM treatment.