title: Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC.
abstract: In order to grow within an immunocompetent host, tumour cells have evolved various strategies to cope with the host's immune system. These strategies include the downregulation of surface molecules and the secretion of immunosuppressive factors like IL-10 and PGE2 that impair the maturation of immune effector cells, among other mechanisms. Recently, tumour exosomes (TEX) have also been implicated in tumour-induced immune suppression as it has been shown that TEX can induce apoptosis in T lymphocytes. In this study, we extend our knowledge about immunosuppressive features of these microvesicles in that we show that TEX efficiently bind and sequester tumour-reactive antibodies and dramatically reduce their binding to tumour cells. Moreover, we demonstrate that this antibody sequestration reduces the antibody-dependent cytotoxicity by immune effector cells, which is among the most important anti-tumour reactions of the immune system and a significant activity of therapeutic antibodies. Taken together, these data point to the fact that tumour-derived exosomes interfere with the tumour-specific function of immune cells and constitute an additional mechanism how tumours escape from immune surveillance.
authors.affiliation: Department of Gene Vectors, Helmholtz Center, Marchioninistrasse 25, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Battke
authors.forename: Romana
authors.initials: R
authors.lastname: Ruiss
authors.forename: Ulrich
authors.initials: U
authors.lastname: Welsch
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.forename: Simon
authors.initials: S
authors.lastname: Jochum
authors.forename: Reinhard
authors.initials: R
authors.lastname: Zeidler
mesh_terms: D000912:Antibodies, Neoplasm / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D000071858:Epithelial Cell Adhesion Molecule; D055354:Exosomes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008854:Microscopy, Electron; D010051:Ovarian Neoplasms / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D019139:Tumor Escape
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D018719:Erb-b2 Receptor Tyrosine Kinases; C499379:EPCAM protein, human; C508053:ERBB2 protein, human