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Dieterich LC, Ikenberg K, Cetintas T, et al. Tumor-Associated Lymphatic Vessels Upregulate PDL1 to Inhibit T-Cell Activation. Front Immunol. 2017;8:66doi: 10.3389/fimmu.2017.00066.
Dieterich, L. C., Ikenberg, K., Cetintas, T., Kapaklikaya, K., Hutmacher, C., & Detmar, M. (2017). Tumor-Associated Lymphatic Vessels Upregulate PDL1 to Inhibit T-Cell Activation. Frontiers in immunology, 866. https://doi.org/10.3389/fimmu.2017.00066
Dieterich, Lothar C, et al. "Tumor-Associated Lymphatic Vessels Upregulate PDL1 to Inhibit T-Cell Activation." Frontiers in immunology vol. 8 (2017): 66. doi: https://doi.org/10.3389/fimmu.2017.00066
Dieterich LC, Ikenberg K, Cetintas T, Kapaklikaya K, Hutmacher C, Detmar M. Tumor-Associated Lymphatic Vessels Upregulate PDL1 to Inhibit T-Cell Activation. Front Immunol. 2017 Feb 03;8:66. doi: 10.3389/fimmu.2017.00066. eCollection 2017. PMID: 28217128; PMCID: PMC5289955.
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Front Immunol. 2017 Feb 03;8:66. doi: 10.3389/fimmu.2017.00066. eCollection 2017.

Tumor-Associated Lymphatic Vessels Upregulate PDL1 to Inhibit T-Cell Activation.

Frontiers in immunology

Lothar C Dieterich, Kristian Ikenberg, Timur Cetintas, Kübra Kapaklikaya, Cornelia Hutmacher, Michael Detmar

Affiliations

  1. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich , Zurich , Switzerland.
  2. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

PMID: 28217128 PMCID: PMC5289955 DOI: 10.3389/fimmu.2017.00066

Abstract

Tumor-associated lymphatic vessels (LVs) play multiple roles during tumor progression, including promotion of metastasis and regulation of antitumor immune responses by delivering antigen from the tumor bed to draining lymph nodes (LNs). Under steady-state conditions, LN resident lymphatic endothelial cells (LECs) have been found to maintain peripheral tolerance by directly inhibiting autoreactive T-cells. Similarly, tumor-associated lymphatic endothelium has been suggested to reduce antitumor T-cell responses, but the mechanisms that mediate this effect have not been clarified. Using two distinct experimental tumor models, we found that tumor-associated LVs gain expression of the T-cell inhibitory molecule PDL1, similar to LN resident LECs, whereas tumor-associated blood vessels downregulate PDL1. The observed lymphatic upregulation of PDL1 was likely due to IFN-g released by stromal cells in the tumor microenvironment. Furthermore, we found that blocking PDL1 results in increased T-cell stimulation by antigen-presenting LECs

Keywords: PD1; T-cell exhaustion; abortive proliferation; immune checkpoint; lymph node; peripheral tolerance; tumor vasculature; tumor-induced immunosuppression

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