Junctional adhesion molecules mediate transendothelial migration of dendritic cell vaccine in cancer immunotherapy. (10th October 2018)

• Record Type: Journal Article
• Authors: Roh, Seung-Eon; Jeong, Yideul; Kang, Myeong-Ho; Bae, Yong-Soo
• Is Part Of: Cancer letters. Volume 434(2018)
• Page Start: 196
• Page End: 205
• Publication Date: 2018-10-10
• Subjects: Mouse bone marrow-derived dendritic cells (BMDCs) -- Human monocyte-derived dendritic cells (MoDCs) -- TEM -- JAM -- JAML -- DC immunotherapy; APC antigen presenting cell -- BMDC bone marrow-derived DC -- CAR coxsackie and adenovirus receptor -- CCL chemokine ligand -- CCR chemokine receptor -- CTL cytotoxic T lymphocyte -- DC dendritic cell -- GM-CSF granulocyte-macrophage colony-stimulating factor -- HUVEC human umbilical vein endothelial cell -- IgSF immunoglobulin superfamily -- imDC immature dendritic cell -- JAM junctional adhesion molecule -- JAML junctional adhesion molecule-like -- LN lymph node -- LPS lipopolysaccharide -- mDC mature dendritic cell -- MoDC monocyte-derived DC -- pDC plasmacytoid DC -- TEM trans-endothelial migration; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.07.029
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: In vitro generated dendritic cells (DCs) have been studied in cancer immunotherapy for decades. However, the detailed molecular mechanism underlying transendothelial migration (TEM) of DC vaccine across the endothelial barrier to regional lymph nodes (LNs) remains largely unknown. Here, we found that junctional adhesion molecule (JAM)-Like (JAML) is involved in the TEM of mouse bone marrow-derived DCs (BMDCs). Treatment with an anti-JAML antibody or JAML knock-down significantly reduced the TEM activity of BMDCs, leading to impairment of DC-based cancer immunotherapy. We found that the interaction of JAML of BMDCs with the coxsackie and adenovirus receptor of endothelial cells plays a crucial role in the TEM of BMDCs. On the other hand, human monocyte-derived DCs (MoDCs) did not express the JAML protein but still showed normal TEM activity. We found that MoDCs express only JAM1 and that the homophilic interaction of JAM1 is essential for MoDC TEM across a HUVEC monolayer. Our findings suggest that specific JAM family members play an important role in the TEM of in vitro -generated mouse and human DCs from the inoculation site to regional LNs in DC-based cancer immunotherapy. Highlights: JAML is involved in the TEM of mouse bone marrow-derived dendritic cells (BMDC). JAML of BMDCs interacts with CAR of endothelial cells for the TEM of BMDCs. DC-based tumor immunotherapy was significantly impaired by JAML blockades. Human monocyte-derived DCs (MoDCs) do not express JAML, but have a TEM activity. MoDC TEM across the endothelial barrier needs the hemophilic interaction of JAM1.