title: Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease Activity in Patients with Head and Neck Cancer.
abstract: Purpose:Head and neck cancers (HNCs) often induce profound immunosuppression, which contributes to disease progression and interferes with immune-based therapies. Body fluids of patients with HNC are enriched in exosomes potentially engaged in negative regulation of antitumor immune responses. The presence and content of exosomes derived from plasma of patients with HNC are evaluated for the ability to induce immune dysfunction and influence disease activity.Experimental Design:Exosomes were isolated by size-exclusion chromatography from plasma of 38 patients with HNC and 14 healthy donors. Morphology, size, numbers, and protein and molecular contents of the recovered exosomes were determined. Coculture assays were performed to measure exosome-mediated effects on functions of normal human lymphocyte subsets and natural killer (NK) cells. The results were correlated with disease stage and activity.Results:The presence, quantity, and molecular content of isolated, plasma-derived exosomes discriminated patients with HNC with active disease (AD) from those with no evident disease (NED) after oncologic therapies. Exosomes of patients with AD were significantly more effective than exosomes of patients with NED in inducing apoptosis of CD8+T cells, suppression of CD4+T-cell proliferation, and upregulation of regulatory T-cell (Treg) suppressor functions (all atP< 0.05). Exosomes of patients with AD also downregulated NKG2D expression levels in NK cells.Conclusions:Exosomes in plasma of patients with HNC carry immunosuppressive molecules and interfere with functions of immune cells. Exosome-induced immune suppression correlates with disease activity in HNC, suggesting that plasma exosomes could be useful as biomarkers of HNC progression.Clin Cancer Res; 23(16); 4843-54. ©2017 AACR.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.|University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Otorhinolaryngology, University of Duisburg-Essen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Ludwig
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Theofanis
authors.initials: T
authors.lastname: Floros
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.|Department of Otorhinolaryngology, Head and Neck Surgery, University of Ulm, Germany.
authors.forename: Marie-Nicole
authors.initials: MN
authors.lastname: Theodoraki
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Chang-Sook
authors.initials: CS
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Jackson
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. whitesidetl@upmc.edu.|University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D055354:Exosomes / Q000276:immunology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D055815:Young Adult