Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment - New Findings and Future Perspectives.

antiangiogenic therapy immunoregulation immunotherapy tumor endothelial cells tumor microenvironment

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2020
Historique:
received: 11 05 2020
accepted: 21 07 2020
entrez: 25 9 2020
pubmed: 26 9 2020
medline: 26 9 2020
Statut: epublish

Résumé

The tumor microenvironment (TME) plays a central role in cancer development and progression. It represents a complex network of cancer cell (sub-)clones and a variety of stromal cell types. Recently, new technology platforms shed light on the cellular composition of the TME at very high resolution and identified a complex landscape of multi-lineage immune cells (e.g., T and B lymphocytes, myeloid cells, and dendritic cells), cancer associated fibroblasts (CAF) and tumor endothelial cells (TECs). A growing body of evidence suggests that metabolically, genetically and on their transcriptomic profile TECs exhibit unique phenotypic and functional characteristics when compared to normal endothelial cells (NECs). Furthermore, the functional role of TECs is multifaceted as they are not only relevant for promoting tumor angiogenesis but have also evolved as key mediators of immune regulation in the TME. Regulatory mechanisms are complex and profoundly impact peripheral immune cell trafficking into the tumor compartment by acting as major gatekeepers of cellular transmigration. Moreover, TECs are associated with T cell priming, activation and proliferation by acting as antigen-presenting cells themselves. TECs are also essential for the formation of tertiary lymphoid structures (TLS) within the tumor, which have recently been associated with treatment response to checkpoint antibody therapy. Further essential characteristics of TECs compared to NECs are their high proliferative potential as well as greatly altered gene expression profile (e.g., upregulation of pro-angiogenic, extracellular matrix remodeling, and stemness genes), which results in enhanced secretion of immunomodulatory cytokines and altered cell-surface receptors [e.g., major histocompatibility complex (MHC) and immune checkpoints]. The TEC phenotype may be rooted in an aggressive tumor micro-milieu based on cellular stress

Identifiants

pubmed: 32974337
doi: 10.3389/fcell.2020.00766
pmc: PMC7466447
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

766

Informations de copyright

Copyright © 2020 Nagl, Horvath, Pircher and Wolf.

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Auteurs

Laurenz Nagl (L)

Department of Internal Medicine V (Haematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.

Lena Horvath (L)

Department of Internal Medicine V (Haematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.

Andreas Pircher (A)

Department of Internal Medicine V (Haematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.

Dominik Wolf (D)

Department of Internal Medicine V (Haematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Tyrolean Cancer Research Institute (TKFI), Innsbruck, Austria.
Department of Oncology, Hematology, Rheumatology and Immunoncology, University Hospital Bonn (UKB), Bonn, Germany.

Classifications MeSH