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PMID: 26155419 Published · epublish English Review Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Understanding high endothelial venules: Lessons for cancer immunology.

Oncoimmunology ·Vol. 4 ·No. 6 ·2015-06-00 ·Pages e1008791

Ager A, May MJ

Abstract

High endothelial venules (HEVs) are blood vessels especially adapted for lymphocyte trafficking which are normally found in secondary lymphoid organs such as lymph nodes (LN) and Peyer's patches. It has long been known that HEVs develop in non-lymphoid organs during chronic inflammation driven by autoimmunity, infection or allografts. More recently, HEVs have been observed in solid, vascularized tumors and their presence correlated with reduced tumor size and improved patient outcome. It is proposed that newly formed HEV promote antitumor immunity by recruiting naive lymphocytes into the tumor, thus allowing the local generation of cancerous tissue-destroying lymphocytes. Understanding how HEVs develop and function are therefore important to unravel their role in human cancers. In LN, HEVs develop during embryonic and early post-natal life and are actively maintained by the LN microenvironment. Systemic blockade of lymphotoxin-β receptor leads to HEV de-differentiation, but the LN components that induce HEV differentiation have remained elusive. Recent elegant studies using gene-targeted mice have demonstrated clearly that triggering the lymphotoxin-β receptor in endothelial cells (EC) induces the differentiation of HEV and that CD11c+ dendritic cells play a crucial role in this process. It will be important to determine whether lymphotoxin-β receptor-dependent signaling in EC drives the development of HEV during tumorigenesis and which cells have HEV-inducer properties. This may reveal therapeutic approaches to promote HEV neogenesis and determine the impact of newly formed HEV on tumor immunity.

Keywords
EC endothelial cells FRC fibroblast reticular cells HEC high endothelial cells HEV high endothelial venules LN lymph nodes LPA lysophosphatidic acid LT lymphotoxin LT-βR lymphotoxin-β receptor MAdCAM mucosal cell adhesion molecule PNAd peripheral node addressin SIP sphingosine-1-phosphate T cell homing TLO tertiary lymphoid organ VE-cadherin vascular endothelial cadherin VEGF vascular endothelial growth factor dendritic cells high endothelial venules lymphotoxin-β receptor tumor immunotherapy
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ager Ann
Infection and Immunity; School of Medicine; Cardiff University ; Cardiff, UK.
May Michael J
School of Veterinary Medicine; University of Pennsylvania ; Philadelphia, PA, USA.
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Article Info
Journal
Oncoimmunology
Abbr.
Oncoimmunology
ISSN
2162-4011
DOI
10.1080/2162402X.2015.1008791
Published
2015-06-00
Epub
2015-00-07
Pages
e1008791
Language
English
Region
United States
NLM ID
101570526
PMCID
PMC4485764
Grants
Medical Research Council · MR/L008742/1 · United Kingdom
NHLBI NIH HHS · R01 HL096642 · United States
External Links
PubMed source DOI: 10.1080/2162402X.2015.1008791 PMC Full Text
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