Oncotarget

Research Papers:

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 _ and Chien-Ho Chen

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Oncotarget. 2015; 6:159-170. https://doi.org/10.18632/oncotarget.2700

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Abstract

Pin-Zhir Chao1,2,*, Ming-Shium Hsieh1,3,*, Chao-Wen Cheng1, Tin-Jui Hsu4, Yun-Tien Lin4, Chang-Hao Lai4, Chen-Chung Liao5, Wei-Yu Chen6, Ting-Kai Leung7, Fei-Peng Lee8, Yung-Feng Lin4 and Chien-Ho Chen4

1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

2 Department of Otolaryngology, Shuang-Ho Hospital, New Taipei, Taiwan

3 Department of Orthopedics, En Chu Kong Hospital, New Taipei, Taiwan

4 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

5 Proteomics Research Center, National Yang-Ming University, Taipei, Taiwan

6 Department of Pathology, Wan Fang Hospital, Taipei, Taiwan

7 Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

8 Department of Otolaryngology, Head and Neck Surgery, Wan-Fang Medical Center, Taipei, Taiwan

* These authors contributed equally to this work

Correspondence:

Yung-Feng Lin, email:

Chien-Ho Chen, email:

Keywords: dendritic cell, DC-SIGN, NPC, annexin A2, IL-10, immunosuppression

Received: September 03, 2014 Accepted: November 06, 2014 Published: November 06, 2014

Abstract

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 mannose-rich 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.


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