Tumor Endothelial Cell-Mediated Antigen-Specific T-cell Suppression via the PD-1/PD-L1 Pathway.

Molecular Cancer Research : MCR
Kazuhiro TaguchiHideki Ohdan

Abstract

Tumor endothelial cells (TEC) play multiple roles in the regional specialization of vascular structure and physiology. Because TECs in the tumor microenvironment come in contact with circulating immune cells, they might influence not only trafficking but also the antitumor cellular immune response. In a mouse tumor implantation model with B16 melanoma cells, TECs expressed MHC class II, costimulating molecules, and programmed death-ligand 1 (PD-L1), suggesting that they are antigen (Ag)-presenting cells with suppressive activity. Furthermore, TECs were able to take up and present tumor-derived ovalbumin (OVA) peptide on MHC class I molecules. In functional assays, B16-OVA tumor-derived TECs significantly suppressed the proliferation and Ag-specific cytotoxicity of OVA-specific CD8+ T cells relative to those of B16 tumor-derived TECs. This suppressive activity required cell-cell contact and was abrogated by PD-L1 blockade. TECs impaired proinflammatory cytokine production of CD8+ T cells, including IL2, TNFα, and IFNγ. B16-OVA tumor-derived TECs induced immunosuppressive CD4+ T cells that suppressed OVA-specific CD8+ T-cell proliferation via inhibitory cytokines, including IL10 and TGFβ. Deficiency of PD-L1 in TECs, but not in h...Continue Reading

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Citations

Nov 5, 2020·International Journal of Molecular Sciences·Priya VeluswamyJens Wippermann
Apr 23, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Marco ChilosiClaudio Doglioni
Apr 20, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yamin LiangDangheng Wei
May 25, 2021·Journal of the American Heart Association·Wei YuanBin Wang
Jul 14, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jinlong LiuZhimeng Wu

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