Dendritic Cells Recognize Tumor-Specific Glycosylation of Carcinoembryonic Antigen on Colorectal Cancer Cells through Dendritic Cell–Specific Intercellular Adhesion Molecule-3–Grabbing Nonintegrin

Gisbergen, Klaas P. J. M. van; Aarnoudse, Corlien A.; Meijer, Gerrit A.; Geijtenbeek, Teunis B. H.; Kooyk, Yvette van

doi:10.1158/0008-5472.can-04-4140

Cited by 157 publications

(145 citation statements)

References 51 publications

(65 reference statements)

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“…Recently, van Gisbergen et al reported that DC-SIGN is involved in the recognition of colorectal cancer cells by DCs through the binding of Le x /Le y carbohydrates on CEA (14). The above data and our previous results (15) indicate that Le a /Le b glycans expressed on colorectal carcinoma cells are also associated with the interaction of DCs with colorectal cancer cells through DC-SIGN recognition.…”

Section: Dc-sign Mediates the Interaction Of Dcs To Primary Colorectasupporting

confidence: 77%

“…Although the identification of colorectal carcinoma cell surface glycoproteins that bind to DC-SIGN was a critical step for identifying the glycoproteins involved in DC-SIGN-mediated suppression, it is important to note that colorectal carcinoma glycoproteins modified by abnormal glycans may bind to DC-SIGN and not to the regular glycans on normal colorectal cells (14). In addition, binding by DC-SIGN was specific for tumor-associated Le glycans on the colorectal carcinomas, because tumor-associated Le glycans were not observed on the HLF hepatoma.…”

Section: Dc-sign Recognizes Tumor-associated Le a /Le B Glycans Of Cementioning

confidence: 99%

“…Several research groups have previously and recently reported that ICAM-2, ICAM-3, Mac-1, CEA, CEACAM1, etc. are cellular ligands (12)(13)(14).…”

Section: Dc-sign Recognizes Tumor-associated Le a /Le B Glycans Of Cementioning

confidence: 99%

“…DC-SIGN functions as an adhesion receptor and mediates the binding and internalization of pathogens such as viruses (HIV and hepatitis C), bacteria (Mycobacterium), fungi, and parasites (1,13). Recently, it was reported that immature DCs use DC-SIGN to adhere to colorectal cancer cells through the recognition of Le x and Le y Ags present on carcinoembryonic Ag (CEA) (14).…”

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confidence: 99%

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Glycosylation-Dependent Interactions of C-Type Lectin DC-SIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells

Nonaka

Yong

Murai

et al. 2008

The Journal of Immunology

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Dendritic cells (DCs) are APCs that play an essential role by bridging innate and adaptive immunity. DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is one of the major C-type lectins expressed on DCs and exhibits high affinity for nonsialylated Lewis (Le) glycans. Recently, we reported the characterization of oligosaccharide ligands expressed on SW1116, a typical human colorectal carcinoma recognized by mannan-binding protein, which is a serum C-type lectin and has similar carbohydrate-recognition specificities as DC-SIGN. These tumor-specific oligosaccharide ligands were shown to comprise clusters of tandem repeats of Lea/Leb epitopes. In this study, we show that DC-SIGN is involved in the interaction of DCs with SW1116 cells through the recognition of aberrantly glycosylated forms of Lea/Leb glycans on carcinoembryonic Ag (CEA) and CEA-related cell adhesion molecule 1 (CEACAM1). DC-SIGN ligands containing Lea/Leb glycans are also highly expressed on primary cancer colon epithelia but not on normal colon epithelia, and DC-SIGN is suggested to be involved in the association between DCs and colorectal cancer cells in situ by DC-SIGN recognizing these cancer-related Le glycan ligands. Furthermore, when monocyte-derived DCs (MoDCs) were cocultured with SW1116 cells, LPS-induced immunosuppressive cytokines such as IL-6 and IL-10 were increased. The effects were significantly suppressed by blocking Abs against DC-SIGN. Strikingly, LPS-induced MoDC maturation was inhibited by supernatants of cocultures with SW1116 cells. Our findings imply that colorectal carcinomas affecting DC function and differentiation through interactions between DC-SIGN and colorectal tumor-associated Le glycans may induce generalized failure of a host to mount an effective antitumor response.

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Section: Dc-sign Mediates the Interaction Of Dcs To Primary Colorectasupporting

confidence: 77%

Section: Dc-sign Recognizes Tumor-associated Le a /Le B Glycans Of Cementioning

confidence: 99%

“…Several research groups have previously and recently reported that ICAM-2, ICAM-3, Mac-1, CEA, CEACAM1, etc. are cellular ligands (12)(13)(14).…”

Section: Dc-sign Recognizes Tumor-associated Le a /Le B Glycans Of Cementioning

confidence: 99%

mentioning

confidence: 99%

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Glycosylation-Dependent Interactions of C-Type Lectin DC-SIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells

Nonaka

Yong

Murai

et al. 2008

The Journal of Immunology

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“…20 The positioning of macrophages in the cutaneous tumor invasion front is not specific for CTCL in the skin because the peritumoral localization of CD209 ϩ macrophages has also been described in cutaneous melanoma. 29 The expression of CD209 has been shown to facilitate recognition of tumor antigens in colorectal cancer 30 and acute lymphoblastic leukemia T cells. 31 The up-regulation of CCL18 in MF was accompanied by increased expression of CCL17 mRNA in our MF patients.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Günther

Zimmermann

Berndt

et al. 2011

The American Journal of Pathology

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Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma (CTCL), which can deteriorate from patch stage to dermal-based tumors and systemic involvement in years. The interaction of chemokines in the skin with CTCL cells might have implications for the pathogenesis of the disease. In this study, we show by PCR analysis and immunofluorescence staining that the chemokine CCL18 is present in skin biopsy specimens of patients with MF and its precursor form parapsoriasis en plaque but not in healthy tissue. In addition, the serum levels of CCL18 were increased threefold in MF patients compared with those in healthy controls. In skin, CCL18 was specifically expressed by CD163 ؉ CD209 ؉ macrophages at the invasive margin of the tumor and not expressed by mature CD208 ؉ dendritic cells in the center of the tumor. The chemokine CCL17 was, by contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells and abolished the CXCL12-induced growth of a CTCL cell line. These data link the increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of the chemokine in the pathogenesis

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Carbohydrates as Unique Structures for Disease Diagnosis

Rittenhouse-Olson

2008

Carbohydrate‐Based Vaccines and Immunotherapies

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Dendritic Cells Recognize Tumor-Specific Glycosylation of Carcinoembryonic Antigen on Colorectal Cancer Cells through Dendritic Cell–Specific Intercellular Adhesion Molecule-3–Grabbing Nonintegrin

Abstract: 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.

Cited by 157 publications

References 51 publications

Glycosylation-Dependent Interactions of C-Type Lectin DC-SIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells

Glycosylation-Dependent Interactions of C-Type Lectin DC-SIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Carbohydrates as Unique Structures for Disease Diagnosis

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