Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin.
Dendritic cells play a pivotal role in the induction of antitumor immune responses. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripheral to the tumor. The majority of colorectal cancers overexpress carcinoembryonic antigen (CEA), and malignant transformation changes the glycosylation of CEA on colon epithelial cells, resulting in higher levels of Lewis(x) and de novo expression of Lewis(y) on tumor-associated CEA. Dendritic cells express the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) that has high affinity for nonsialylated Lewis antigens, so we hypothesized that DC-SIGN is involved in recognition of colorectal cancer cells by dendritic cells. We show that immature dendritic cells within colorectal cancer express DC-SIGN and that immature dendritic cells but not mature dendritic cells interact with tumor cells. DC-SIGN mediates these interactions through binding of Lewis(x) and Lewis(y) carbohydrates on CEA of colorectal cancer cells. In contrast, DC-SIGN does not bind CEA expressed on normal colon epithelium that contains low levels of Lewis antigens. This indicates that dendritic cells may recognize colorectal cancer cells through binding of DC-SIGN to tumor-specific glycosylation on CEA. Similar to pathogens that target DC-SIGN to escape immunosurveillance, tumor cells may interact with DC-SIGN to suppress dendritic cell functions.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands.
Klaas P J M
KP
van Gisbergen
Corlien A
CA
Aarnoudse
Gerrit A
GA
Meijer
Teunis B H
TB
Geijtenbeek
Yvette
Y
van Kooyk
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D007983:Lewis Blood Group Antigens / Q000276:immunology / Q000378:metabolism; D016256:Lewis X Antigen / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D000943:Antigens, Differentiation; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C069847:CD66 antigens; C094162:Lewis Y antigen