title: Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance.
abstract: Alteration of the surface glycosylation pattern on malignant cells potentially affects tumor immunity by directly influencing interactions with glycan-binding proteins (lectins) on the surface of immunomodulatory cells. The sialic acid-binding Ig-like lectins Siglec-7 and -9 are MHC class I-independent inhibitory receptors on human NK cells that recognize sialic acid-containing carbohydrates. Here, we found that the presence of Siglec-9 defined a subset of cytotoxic NK cells with a mature phenotype and enhanced chemotactic potential. Interestingly, this Siglec-9+ NK cell population was reduced in the peripheral blood of cancer patients. Broad analysis of primary tumor samples revealed that ligands of Siglec-7 and -9 were expressed on human cancer cells of different histological types. Expression of Siglec-7 and -9 ligands was associated with susceptibility of NK cell-sensitive tumor cells and, unexpectedly, of presumably NK cell-resistant tumor cells to NK cell-mediated cytotoxicity. Together, these observations have direct implications for NK cell-based therapies and highlight the requirement to consider both MHC class I haplotype and tumor-specific glycosylation.
authors.forename: Camilla
authors.initials: C
authors.lastname: Jandus
authors.forename: Kayluz Frias
authors.initials: KF
authors.lastname: Boligan
authors.forename: Obinna
authors.initials: O
authors.lastname: Chijioke
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.forename: Meike
authors.initials: M
authors.lastname: Dahlhaus
authors.forename: Thomas
authors.initials: T
authors.lastname: Démoulins
authors.forename: Christoph
authors.initials: C
authors.lastname: Schneider
authors.forename: Marc
authors.initials: M
authors.lastname: Wehrli
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hunger
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Baerlocher
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.forename: Stephan
authors.initials: S
authors.lastname: von Gunten
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D037102:Lectins / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000276:immunology*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015295:Antigens, Tumor-Associated, Carbohydrate; D037102:Lectins; D008024:Ligands; C402206:SIGLEC7 protein, human; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins