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<p>Paclitaxel and nab-paclitaxel differ in therapeutic efficacy and modulation of the tumor immune microenvironment, yet the molecular basis remains poorly defined. Here, based on a meta-analysis, we first show that treatment with nab-paclitaxel results in a higher overall response rate and pathological complete response compared to paclitaxel in female patients with breast cancer. Notably, TREM2 expression in macrophages is elevated in primary tumors of paclitaxel- but not nab-paclitaxel-treated female patients. In metastatic breast cancer, TREM2<sup>+</sup> macrophage infiltration is increased in primary tumors. In breast cancer models in female mice, paclitaxel, but not nab-paclitaxel, promotes lung metastasis by recruiting TREM2<sup>+</sup> macrophages to primary tumors. Mechanistically, paclitaxel enhances the ATF3-FGF2 axis in breast cancer cells; secreted FGF2 activates the EGR1-TREM2-EMT cytokine axis in macrophages. Genetic ablation of Trem2 or pharmacologic targeting with antisense oligonucleotides suppress paclitaxel-induced breast cancer lung metastasis in vivo. Collectively, our findings demonstrate that paclitaxel, but not nab-paclitaxel, stimulates TREM2 expression and expands TREM2<sup>+</sup> macrophages, suggesting that TREM2 targeting could enhance paclitaxel efficacy while limiting metastasis.</p>

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Paclitaxel drives TREM2+ macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月3日

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  • Yuqi Xing,
  • Ruiqi Zhong,
  • Qianchen Li,
  • Xinwei Duan,
  • Moyang Xu,
  • Miao Yu,
  • Chenying Liu,
  • Junming He,
  • Yi Sun,
  • Yunling Wang,
  • Xiaojing Guo,
  • Yunfei Xu,
  • Hongnan Mo,
  • Fei Ma,
  • Hongquan Zhang,
  • Jun Zhan

摘要

Paclitaxel and nab-paclitaxel differ in therapeutic efficacy and modulation of the tumor immune microenvironment, yet the molecular basis remains poorly defined. Here, based on a meta-analysis, we first show that treatment with nab-paclitaxel results in a higher overall response rate and pathological complete response compared to paclitaxel in female patients with breast cancer. Notably, TREM2 expression in macrophages is elevated in primary tumors of paclitaxel- but not nab-paclitaxel-treated female patients. In metastatic breast cancer, TREM2+ macrophage infiltration is increased in primary tumors. In breast cancer models in female mice, paclitaxel, but not nab-paclitaxel, promotes lung metastasis by recruiting TREM2+ macrophages to primary tumors. Mechanistically, paclitaxel enhances the ATF3-FGF2 axis in breast cancer cells; secreted FGF2 activates the EGR1-TREM2-EMT cytokine axis in macrophages. Genetic ablation of Trem2 or pharmacologic targeting with antisense oligonucleotides suppress paclitaxel-induced breast cancer lung metastasis in vivo. Collectively, our findings demonstrate that paclitaxel, but not nab-paclitaxel, stimulates TREM2 expression and expands TREM2+ macrophages, suggesting that TREM2 targeting could enhance paclitaxel efficacy while limiting metastasis.