Dendritic cells respond to nasopharygeal carcinoma cells through annexin A2-recognizing DC-SIGN

Pin Zhir Chao, Ming Shium Hsieh, Chao Wen Cheng, Tin Jui Hsu, Yun Tien Lin, Chang Hao Lai, Chen Chung Liao, Wei Yu Chen, Ting Kai Leung, Fei Peng Lee, Yung Feng Lin*, Chien Ho Chen

*此作品的通信作者

研究成果: Article同行評審

22 引文 斯高帕斯(Scopus)

摘要

Dendritic cells (DCs) play an essential role in immunity and are used in cancer immunotherapy. However, these cells can be tuned by tumors with immunosuppressive responses. DC-specific intercellular adhesion molecule 3-Grabbing Nonintegrin (DC-SIGN), a C-type lectin expressed on DCs, recognizes certain carbohydrate structures which can be found on cancer cells. Nasopharyngeal carcinoma (NPC) is an epithelial cell-derived malignant tumor, in which immune response remains unclear. This research is to reveal the molecular link on NPC cells that induces the immunosuppressive responses in DCs. In this article, we report identification of annexin A2 (ANXA2) on NPC cells as a ligand for DC-SIGN on DCs. N-linked mannoserich glycan on ANXA2 may mediate the interaction. ANXA2 was abundantly expressed in NPC, and knockdown of ANXA2 suppressed NPC xenograft in mice, suggesting a crucial role of ANXA2 in NPC growth. Interaction with NPC cells caused DC-SIGN activation in DCs. Consequently DC maturation and the proinflammatory interleukin (IL)-12 production were inhibited, and the immunosuppressive IL-10 production was promoted. Blockage of either DC-SIGN or ANXA2 eliminated the production of IL- 10 from DCs. This report suggests that suppression of ANXA2 at its expression or glycosylation on NPC may improve DC-mediated immunotherapy for the tumor.

原文English
頁(從 - 到)159-170
頁數12
期刊Oncotarget
6
發行號1
DOIs
出版狀態Published - 2015

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