title: Co-culture of head and neck squamous cell carcinoma spheroids with autologous monocytes predicts prognosis.
abstract: Co-culture of monocytes with autologous fragment (F) spheroids originating from malignant (M) tumour or benign (B) control mucosa of head and neck squamous cell carcinoma (HNSCC) yields interleukin (IL)-6 and monocyte chemo-attractant protein (MCP)-1 secretion. This study investigates the association between this cytokine co-culture response and prognosis. Analysis of IL-6 and MCP-1 content of supernatants from monocytes in vitro co-culture with autologous MF- or BF-spheroids was investigated in a cohort of HNSCC patients (n = 65) diagnosed between 1998 and 2005, all of whom were treated with curative intent by primary surgery. The IL-6 response was expressed as a fraction of the lipopolysaccharid response of the same batch of monocytes. Recurrence, survival and causes of death were then established following the second part of 2005. MCP-1 levels did not predict prognosis. We found that increased levels of IL-6 from autologous monocytes in co-culture with MF-spheroids predicted recurrence with a hazard ratio (HR) of 1.5 [confidence interval (CI): 1.01-2.60; P = 0.05] and co-culture with BF-spheroids and monocytes predicted recurrence (HR = 4.17; CI: 1.54-11.29; P = 0.005). The same results where obtained in addition with TNM stage of the patients. Simultaneous analysis of BF- and MF-spheroid co-culture IL-6 responses as well as adjustment for age and TNM stage of the patients allowed prediction of total survival (HR = 3.1; CI: 1.11-8.56; P = 0.03) based on BF co-culture levels. IL-6 secreted upon in vitro co-culture with monocytes and BF-spheroids predicts recurrence and prognosis, whereas co-culture with monocytes and MF-spheroids predicts recurrence.
authors.affiliation: Section for Otorhinolaryngology/Head and Neck Surgery, Department of Surgical Sciences, Broegelmann Research Laboratory, Haukeland University Hospital, Bergen, Norway. kkro@skno.azm.nl
authors.forename: K W
authors.initials: KW
authors.lastname: Kross
authors.forename: J H
authors.initials: JH
authors.lastname: Heimdal
authors.forename: C
authors.initials: C
authors.lastname: Olsnes
authors.forename: J
authors.initials: J
authors.lastname: Olofsson
authors.forename: H J
authors.initials: HJ
authors.lastname: Aarstad
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000276:immunology*; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D012008:Recurrence; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6