title: In Vitro-Stimulated IL-6 Monocyte Secretion and In Vivo Peripheral Blood T Lymphocyte Activation Uniquely Predicted 15-Year Survival in Patients with Head and Neck Squamous Cell Carcinoma.
abstract: The study was performed in order to determine whether peripheral blood monocyte in vitro function, and lymphocyte in vivo activation at diagnosis, was associated with HPV tumor infection status and 15-year survival in head and neck squamous cell carcinoma (HNSCC) patients. Sixty-five patients from a consecutive cohort of newly diagnosed HNSCCs, together with 18 control patients, were included in the study. Monocyte responsiveness was assessed by measuring monocyte in vitro interleukin (IL)-6 secretions after 24 hours of LPS stimulation in cultures with a serum-free medium. T lymphocyte activation was determined as the fraction of CD71-positive cells on CD3-positive cells by flow cytometry, whereas HPV infection was determined by PCR on formalin-fixed paraffin-embedded (FFPE) tumor tissue. Disease-specific survivals and overall survivals were determined 15 years following inclusion. HPV-positive HNSCC patients had a lower monocyte LPS-stimulated IL-6 response. A high LPS-stimulated monocyte IL-6 response predicted a decreased survival rate (P=0.019). A high percentage of CD71-positive T lymphocytes also predicted an impaired prognosis (P=0.021). The predictive power of IL-6 monocyte LPS-stimulated responses was retained when adjusted for age, gender and TNM stage of the patients. The monocyte and T lymphocyte survival predictions were independent of each other. The survival was particularly low with a combined high activated monocyte and T lymphocyte status. In a multivariate analysis, IL-6 secretion and the percentage of CD71-positive T lymphocytes both uniquely predicted survival independent of HPV infection status. It is postulated that the natural and adaptive immune systems are separately and additionally linked to the clinical aggressiveness of HNSCCs.
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: Helene Hersvik
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: Olav Karsten
authors.initials: OK
authors.lastname: Vintermyr
authors.affiliation: Department of Microbiology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Elling
authors.initials: E
authors.lastname: Ulvestad
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Kenneth
authors.initials: K
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: John Helge
authors.initials: JH
authors.lastname: Heimdal
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: Hans Jorgen
authors.initials: HJ
authors.lastname: Aarstad
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000276:immunology* / Q000401:mortality; D002478:Cells, Cultured; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000150:complications / Q000276:immunology* / Q000401:mortality; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D011379:Prognosis; D011990:Receptors, Transferrin / Q000276:immunology / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; C068126:CD71 antigen; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011990:Receptors, Transferrin