title: Tumor-expressed collagens can modulate immune cell function through the inhibitory collagen receptor LAIR-1.
abstract: Many tumor types over-express collagens, what correlates with enhanced metastatic capacity and unfavorable clinical outcome. This is generally explained by the importance of collagens in creating a microenvironment that supports tumor cell survival and enhances cell migration. Importantly, collagens act as ligands for the inhibitory receptor LAIR-1, which inhibits the function of multiple types of immune cells. Here we propose a new role for tumor expressed collagens and show that these structural proteins can be exploited by tumor cells to inhibit immune responses through an interaction with LAIR-1. We show that both LAIR-1-Fc fusion proteins and LAIR-1 expressing cells bind to transmembrane collagens expressed by tumor cells. Interference with collagen expression by specific knock-down of prolyl 4-hydroxylase diminishes LAIR-1 binding to tumor cells, demonstrating the specificity of the interaction. Consistently, both transmembrane collagens and extracellular collagens produced by multiple tumor cell types can activate LAIR-1. Furthermore, overexpression of collagen XVII on target cells results in diminished NK cell cytotoxic activity. Thus tumor-expressed collagens can bind and trigger immune inhibitory signaling via LAIR-1, suggesting that collagens indeed may affect tumor immune evasion.
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Tomasz P
authors.initials: TP
authors.lastname: Rygiel
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Stolte
authors.forename: Talitha
authors.initials: T
authors.lastname: de Ruiter
authors.forename: Michael L
authors.initials: ML
authors.lastname: van de Weijer
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003094:Collagen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; D003094:Collagen