Dendritic cells respond to nasopharygeal carcinoma cells through annexin A2-recognizing DC-SIGN.
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.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Department of Otolaryngology, Shuang-Ho Hospital, New Taipei, Taiwan.
Pin-Zhir
PZ
Chao
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Department of Orthopedics, En Chu Kong Hospital, New Taipei, Taiwan.
Ming-Shium
MS
Hsieh
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chao-Wen
CW
Cheng
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Tin-Jui
TJ
Hsu
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Yun-Tien
YT
Lin
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Chang-Hao
CH
Lai
Proteomics Research Center, National Yang-Ming University, Taipei, Taiwan.
Chen-Chung
CC
Liao
Department of Pathology, Wan Fang Hospital, Taipei, Taiwan.
Wei-Yu
WY
Chen
Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ting-Kai
TK
Leung
Department of Otolaryngology, Head and Neck Surgery, Wan-Fang Medical Center, Taipei, Taiwan.
Fei-Peng
FP
Lee
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Yung-Feng
YF
Lin
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Chien-Ho
CH
Chen
D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D002277:Carcinoma; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D047468:Immunoprecipitation; D007166:Immunosuppressive Agents / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009368:Neoplasm Transplantation; D011134:Polysaccharides / Q000737:chemistry; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D017306:Annexin A2; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12; D037181:Lectins, C-Type; D008024:Ligands; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C472822:ANXA2 protein, human