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Background <p>PD-1 inhibitors are a promising treatment for melanoma, but over 50% of patients with metastatic melanoma do not respond well. This limited efficacy is partly due to the aberrant vascular structure and immunosuppressive microenvironment in metastatic lung tissue.</p> Methods <p>We developed an extracellular vesicle-based delivery system Tanshinone IIA &amp; Icaritin -MPs (TSA&amp;ICT-MPs) that targets lung metastases. In vivo in vitro models, cell experiments, immunofluorescence, immunohistochemistry, flow cytometry, and mass spectrometry flow cytometry were used to validate the efficacy of TSA&amp;ICT-MPs in promoting vascular normalization, enhancing the activity of tumor-infiltrating lymphocytes (TILs), and reducing myeloid-derived inhibitory cell (MDSC) infiltration by modulating the adenosine metabolic pathway.</p> Results <p>TSA&amp;ICT-MP contributes to vascular normalization by modulating ELTD1, thereby enhancing TIL infiltration, and reduces adenosine release by targeting ENPP1, thus enhancing anti-tumor immunity. Combining TSA&amp;ICT-MP with α-PD-1 achieved a 70.33% suppression rate of lung metastasis and prolonged survival in murine models. This approach offers a promising strategy to enhance the efficacy of melanoma immunotherapy.</p> Graphical abstract <p></p>

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Tanshinone IIA&Icaritin -MPs regulated vascular normalization and restored tumor-infiltrating T lymphocyte function to boost anti-PD-1 therapy in melanoma lung metastasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月27日

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  • Xiaoyu Che,
  • Yaqin Li,
  • Wenjing Chen,
  • Xinyu Yang,
  • Hong Wang,
  • Shan Deng,
  • Xiaoqi Li,
  • Xiaoying Qin,
  • Yan Chen,
  • Yuping Liu

摘要

Background

PD-1 inhibitors are a promising treatment for melanoma, but over 50% of patients with metastatic melanoma do not respond well. This limited efficacy is partly due to the aberrant vascular structure and immunosuppressive microenvironment in metastatic lung tissue.

Methods

We developed an extracellular vesicle-based delivery system Tanshinone IIA & Icaritin -MPs (TSA&ICT-MPs) that targets lung metastases. In vivo in vitro models, cell experiments, immunofluorescence, immunohistochemistry, flow cytometry, and mass spectrometry flow cytometry were used to validate the efficacy of TSA&ICT-MPs in promoting vascular normalization, enhancing the activity of tumor-infiltrating lymphocytes (TILs), and reducing myeloid-derived inhibitory cell (MDSC) infiltration by modulating the adenosine metabolic pathway.

Results

TSA&ICT-MP contributes to vascular normalization by modulating ELTD1, thereby enhancing TIL infiltration, and reduces adenosine release by targeting ENPP1, thus enhancing anti-tumor immunity. Combining TSA&ICT-MP with α-PD-1 achieved a 70.33% suppression rate of lung metastasis and prolonged survival in murine models. This approach offers a promising strategy to enhance the efficacy of melanoma immunotherapy.

Graphical abstract