title: In vitro Monocyte IL-6 Secretion Levels Following Stimulation with Autologous Spheroids Derived from Tumour or Benign Mucosa Predict Long-term Survival in Head and Neck Squamous Cell Carcinoma Patients.
abstract: MCP-1/IL-6 in vitro monocyte secretion upon coculture with autologous fragment spheroids was studied in relation to patient 5- and 10-year overall survival rates in head and neck squamous cell carcinoma (HNSCC) patients (n = 65) diagnosed between 1998 and 2005, nine of whom had an human papilloma virus (HPV) tumour infection. The spheroids were harvested from malignant or benign tissue during primary surgery. Two weeks following surgery, freshly isolated autologous monocytes and benign or malignant spheroids were cocultured 24 h in vitro. The IL-6 secretion was expressed as a fraction of the lipopolysaccharide (LPS) response from the same batch of monocytes. HPV status was obtained by employing PCR analyses of primary diagnostic blocks. IL-6/MCP-1 response levels were not found to be dependent on HPV infection status. MCP-1 secretion did not predict prognosis, nor did in vitro IL-6 monocyte background or LPS-stimulated IL-6 secretion. At 5-year observation, dichotomized IL-6 levels following monocyte coculture, with both malignant and benign spheroids, showed a strong trend towards predicting survival, that is a low monocyte malignant coculture response showed a survival of 31 ± 17 versus 58 ± 17% with a high such response (P = 0.057). When studying monocyte IL-6 coculture responses evaluating benign and malignant spheroid results statistically together, a prediction of survival up to 10 years was found (hazard ratio = 0.48; confidence interval = 0.24-0.96; P < 0.05) with double low IL-6 responses. This survival prediction was also present after an adjustment for HPV tumour infection status. In conclusion, monocyte IL-6 in vitro secretion in cocultures with autologous spheroids/serum from HNSCCs predicted 5- and 10-year survivals, both with and without tumour HPV tumour adjustment.
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: H J
authors.initials: HJ
authors.lastname: Aarstad
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: H H
authors.initials: HH
authors.lastname: Aarstad
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: O K
authors.initials: OK
authors.lastname: Vintermyr
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: K W
authors.initials: KW
authors.lastname: Kross
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Lybak
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: J-H
authors.initials: JH
authors.lastname: Heimdal
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000401:mortality; D018932:Chemokine CCL2 / Q000378:metabolism*; D018920:Coculture Techniques; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000401:mortality; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology; D030361:Papillomavirus Infections / Q000821:virology; D011379:Prognosis; D018874:Spheroids, Cellular / Q000276:immunology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides