Exosomes of Epstein-Barr Virus-Associated Gastric Carcinoma Suppress Dendritic Cell Maturation

被引:32
作者
Hinata, Munetoshi [1 ]
Kunita, Akiko [1 ]
Abe, Hiroyuki [1 ]
Morishita, Yasuyuki [1 ]
Sakuma, Kei [1 ]
Yamashita, Hiroharu [2 ]
Seto, Yasuyuki [2 ]
Ushiku, Tetsuo [1 ]
Fukayama, Masashi [1 ,3 ]
机构
[1] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo 1130033, Japan
[2] Univ Tokyo, Grad Sch Med, Dept Gastrointestinal Surg, Tokyo 1130033, Japan
[3] Asahi Gen Hosp, Asahi TelePathol Ctr, Chiba 2892511, Japan
基金
日本学术振兴会;
关键词
Epstein-Barr virus; gastric cancer; exosome; dendritic cells; MICROENVIRONMENT; INFILTRATION;
D O I
10.3390/microorganisms8111776
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is characterized by the infiltration of lymphocytes and a unique tumor microenvironment. Exosomes from cancer cells are essential for intercellular communication. The aims of this study were to investigate the secretion of EBVaGC exosomes and their physiological effect on dendritic cell maturation in vitro and to characterize dendritic cells (DCs) in EBVaGC in vivo. Western blotting analysis of CD63 and CD81 of exosomes from EBV-infected gastric cancer cell lines indicated an increase in exosome secretion. The fraction of monocyte-derived DCs positive for the maturation marker CD86 was significantly suppressed when incubated with exosomes from EBV-infected gastric cancer cell lines. Immunohistochemical analysis of GC tissues expressing DC markers (S100, Langerin, CD1a, CD83, CD86, and BDCA-2) indicated that the density of DCs was generally higher in EBVaGC than in EBV-negative GC, although the numbers of CD83- and CD86-positive DCs were decreased in the group with high numbers of CD1a-positive DCs. A low number of CD83-positive DCs was marginally correlated with worse prognosis of EBVaGC in patients. EBVaGC is a tumor with abundant DCs, including immature and mature DCs. Moreover, the maturation of DCs is suppressed by exosomes from EBV-infected epithelial cells.
引用
收藏
页码:1 / 15
页数:15
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