articleCancer CellFeb 3, 2022HYBRID OA

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

AAAssia AsrirCTClaire TardiveauJCJuliette CoudertRLRobin LaffontLBLucas Blanchard

Centre National de la Recherche Scientifique · Université Toulouse III - Paul Sabatier · +7 more institutions

PubMed
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Abstract

Recruitment of lymphocytes into tumors is critical for anti-tumor immunity and efficacious immunotherapy. We show in murine models that tumor-associated high endothelial venules (TA-HEVs) are major sites of lymphocyte entry into tumors at baseline and upon treatment with anti-PD-1/anti-CTLA-4 immune checkpoint blockade (ICB). TA-HEV endothelial cells (TA-HECs) derive from post-capillary venules, co-express MECA-79+ HEV sialomucins and E/P-selectins, and are associated with homing and infiltration into tumors of various T cell subsets. Intravital microscopy further shows that TA-HEVs are the main sites of lymphocyte arrest and extravasation into ICB-treated tumors. Increasing TA-HEC frequency and maturation…

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Topics & keywords

Topics
Keywords
  • High endothelial venules
  • Immunotherapy
  • Immunology
  • Cancer research
  • CD8
  • Intravital microscopy
  • Immune checkpoint
  • Melanoma
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