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<p>Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy characterized by profound resistance to immunotherapy. Converting immunologically “cold” tumors into “hot” tumors by enhancing T cell infiltration represents a promising therapeutic strategy, yet the vascular mechanisms regulating immune recruitment in PDAC remain poorly defined. Here, we integrated single-cell RNA sequencing with GEPIA analysis and spatial transcriptomics to investigate the functional role of Ras Interacting Protein 1 (<i>RASIP1</i>)-positive endothelial cells in PDAC. We identified <i>RASIP1</i>-positive tumor endothelial cells as a distinct endothelial subpopulation enriched in leukocyte transendothelial migration pathways, with upregulated adhesion molecules and spatial co-localization with T-effector and <i>IFN</i>-γ signatures. Multiplex immunohistochemistry of human PDAC tissues revealed prominent perivascular accumulation of CD8⁺/GranzymeB⁺ cytotoxic T lymphocytes surrounding <i>RASIP1</i>-positive vessels. Mechanistically, <i>RASIP1</i> knockdown reduced <i>ICAM1</i> expression, whereas <i>RASIP1</i> overexpression enhanced <i>ICAM1</i> signaling, and both modulated <i>ERK</i> phosphorylation dynamics, suggesting that <i>RASIP1</i> regulates endothelial functionality through <i>ERK</i>-related signaling. Collectively, our findings identify a distinct endothelial state that actively shapes the immune microenvironment of PDAC. Targeting <i>RASIP1</i>-positive endothelial cells may represent a potential strategy to enhance tumor immunogenicity and improve responsiveness to immunotherapy.</p>

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RASIP1-positive TECs in pancreatic adenocarcinoma: a potential novel type of endothelial cells correlated with “hot” tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月4日

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  • Shubin Zhang,
  • Yujian He,
  • He Chang,
  • Yuyao Tian,
  • Xin Wang,
  • Zhijie Feng,
  • Wei Qi,
  • Jianhua Liu

摘要

Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy characterized by profound resistance to immunotherapy. Converting immunologically “cold” tumors into “hot” tumors by enhancing T cell infiltration represents a promising therapeutic strategy, yet the vascular mechanisms regulating immune recruitment in PDAC remain poorly defined. Here, we integrated single-cell RNA sequencing with GEPIA analysis and spatial transcriptomics to investigate the functional role of Ras Interacting Protein 1 (RASIP1)-positive endothelial cells in PDAC. We identified RASIP1-positive tumor endothelial cells as a distinct endothelial subpopulation enriched in leukocyte transendothelial migration pathways, with upregulated adhesion molecules and spatial co-localization with T-effector and IFN-γ signatures. Multiplex immunohistochemistry of human PDAC tissues revealed prominent perivascular accumulation of CD8⁺/GranzymeB⁺ cytotoxic T lymphocytes surrounding RASIP1-positive vessels. Mechanistically, RASIP1 knockdown reduced ICAM1 expression, whereas RASIP1 overexpression enhanced ICAM1 signaling, and both modulated ERK phosphorylation dynamics, suggesting that RASIP1 regulates endothelial functionality through ERK-related signaling. Collectively, our findings identify a distinct endothelial state that actively shapes the immune microenvironment of PDAC. Targeting RASIP1-positive endothelial cells may represent a potential strategy to enhance tumor immunogenicity and improve responsiveness to immunotherapy.