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<p>Immunosuppressive myeloid cells, including immature dendritic cells (DC) and tumor-promoting macrophages, drive tumor progression and immune evasion. Reprogramming these cells into immune effectors remains challenging. Here, we present a programmable nanomicelle platform that reconfigures myeloid immunity to combat both primary and metastatic breast cancer (BC). The nanomicelles co-deliver photosensitizers (IR825), anti-PD-L1 antibodies, and antagomiR-182 with spatiotemporal precision. Upon activation, they induce immunogenic cell death, promoting DC maturation to enhance antigen presentation. Concurrently, miR-182 inhibition repolarizes M2-like macrophages into M1-like phenotypes via the TLR4/MYD88/NF-κB pathway. This dual reprogramming enhances CD8<sup>+</sup> T cell infiltration and functionality, driving durable anti-tumor responses. In multiple BC models, the platform suppresses tumor growth, prevents metastasis, and induces long-term immune memory. Its efficacy and immunomodulatory effects were further validated in a patient-derived tumor fragment assay and patient-derived xenograft models, highlighting translational potential. This work offers a clinically relevant strategy to rewire tumor-promoting myeloid cells for cancer immunotherapy.</p>

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Programmable nanomicelles rewire myeloid immunity for durable control of primary and metastatic breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月17日

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  • Jie Yang,
  • Di Chang,
  • Yingbo Li,
  • Zuoyu Xu,
  • Daoshuang Li,
  • Xiaoxuan Xu,
  • Zhiqi Zhang,
  • Yize Li,
  • Jianqiong Zhang,
  • Jinbing Xie,
  • Zebin Xiao,
  • Shenghong Ju

摘要

Immunosuppressive myeloid cells, including immature dendritic cells (DC) and tumor-promoting macrophages, drive tumor progression and immune evasion. Reprogramming these cells into immune effectors remains challenging. Here, we present a programmable nanomicelle platform that reconfigures myeloid immunity to combat both primary and metastatic breast cancer (BC). The nanomicelles co-deliver photosensitizers (IR825), anti-PD-L1 antibodies, and antagomiR-182 with spatiotemporal precision. Upon activation, they induce immunogenic cell death, promoting DC maturation to enhance antigen presentation. Concurrently, miR-182 inhibition repolarizes M2-like macrophages into M1-like phenotypes via the TLR4/MYD88/NF-κB pathway. This dual reprogramming enhances CD8+ T cell infiltration and functionality, driving durable anti-tumor responses. In multiple BC models, the platform suppresses tumor growth, prevents metastasis, and induces long-term immune memory. Its efficacy and immunomodulatory effects were further validated in a patient-derived tumor fragment assay and patient-derived xenograft models, highlighting translational potential. This work offers a clinically relevant strategy to rewire tumor-promoting myeloid cells for cancer immunotherapy.