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Biosynthesis and Functional Significance of Peripheral Node Addressin in Cancer-Associated TLO.
Aliyah M Weinstein1, Walter J Storkus2
1Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA , USA.
Frontiers in Immunology
|August 25, 2016
Summary
Peripheral Node Addressin (PNAd) is a glycoprotein crucial for lymphocyte trafficking to lymphoid organs and tertiary lymphoid structures (TLOs). PNAd is a promising biomarker in cancer, indicating improved prognosis and aiding antitumor immunity.
Area of Science:
- Immunology
- Glycobiology
- Cancer Biology
Background:
- Peripheral Node Addressin (PNAd) is a key molecule on high endothelial venules (HEV) essential for lymphocyte homing to secondary lymphoid organs.
- PNAd functions as the ligand for L-selectin, mediating leukocyte rolling on endothelial surfaces.
- Recent research highlights PNAd's role in tertiary lymphoid organ (TLO) formation within chronic inflammatory sites, including the tumor microenvironment.
Purpose of the Study:
- To review the pathways regulating PNAd biosynthesis in HEV endothelial cells.
- To examine the formation and maintenance of lymphoid structures, particularly TLOs, in the context of cancer.
- To discuss the significance of PNAd as a biomarker and therapeutic target in cancer.
Main Methods:
- Review of existing literature on PNAd, HEV, TLOs, and cancer immunology.
- Analysis of studies investigating PNAd's role in immune cell recruitment and lymphoid neogenesis.
- Examination of preclinical and clinical data on PNAd as a prognostic biomarker in cancer.
Main Results:
- PNAd is a sulfated and fucosylated glycoprotein recognized by MECA-79, acting as the L-selectin ligand.
- TLOs, marked by PNAd, are sites of local adaptive immune cell priming in inflamed tissues, including tumors.
- PNAd has been identified as a biomarker of improved prognosis in human and murine cancers.
- Blockade of PNAd or L-selectin impairs protective antitumor immunity in murine models.
Conclusions:
- PNAd plays a critical role in lymphocyte trafficking and the formation of functional lymphoid structures in both normal and pathological conditions.
- PNAd serves as a valuable biomarker for predicting disease prognosis and a potential therapeutic target in cancer.
- Understanding PNAd biosynthesis and its role in TLOs offers insights into enhancing antitumor immunity.
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