title: Invariant Natural Killer T Cell Deficiency and Functional Impairment in Sleep Apnea: Links to Cancer Comorbidity.
abstract: OBJECTIVE
  Emerging evidence links obstructive sleep apnea (OSA) with increased cancer incidence and mortality. Invariant natural killer T (iNKT) cells play an important role in cancer immunity. We hypothesized that patients with OSA have low number of circulating invariant natural killer T (iNKT) cells, which may also be functionally impaired. This study aims to evaluate the frequency of circulating iNKT cells in OSA.
  
  
  METHODS
  We evaluated the frequency of circulating iNKT cells by flow cytometry in 33 snorers being assessed for possible OSA. Using iNKT cell lines, we also evaluated the effect of exposure to hypoxia over 24 hours on apoptosis, cytotoxicity, and cytokine production.
  
  
  METHODS
  Teaching hospital based sleep unit and research laboratory.
  
  
  METHODS
  Thirty-three snorers were evaluated: 9 with no OSA (apnea-hypopnea frequency [AHI] < 5/h), 12 with mild-moderate OSA (AHI 5-30) and 12 with severe OSA (AHI > 30).
  
  
  RESULTS
  Patients with severe OSA had considerably fewer iNKT cells (0.18%) compared to patients with mild-moderate (0.24%) or no OSA (0.35%), P = 0.0026. The frequency of iNKT cells correlated negatively with apnea-hypopnea index (r = -0.58, P = 0.001), oxygen desaturation index (r = -0.58, P = 0.0003), and SpO2% < 90% (r = -0.5407, P = 0.005). The frequency of iNKT cells increased following 12 months of nCPAP therapy (P = 0.015). Hypoxia resulted in increased apoptosis (P = 0.016) and impaired cytotoxicity (P = 0.035).
  
  
  CONCLUSIONS
  Patients with obstructive sleep apnea (OSA) have significantly reduced levels of circulating invariant natural killer T (iNKT) cells and hypoxia leads to impaired iNKT cell function. These observations may partly explain the increased cancer risk reported in patients with OSA.
authors.affiliation: Obesity Immunology Group, Education & Research Center, St Vincent's University Hospital, University College Dublin, Dublin, Ireland.
authors.forename: Gadintshware
authors.initials: G
authors.lastname: Gaoatswe
authors.affiliation: Pulmonary and Sleep Disorders Unit, St Vincent's University Hospital, Dublin, and School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kent
authors.affiliation: Obesity Immunology Group, Education & Research Center, St Vincent's University Hospital, University College Dublin, Dublin, Ireland.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Corrigan
authors.affiliation: Pulmonary and Sleep Disorders Unit, St Vincent's University Hospital, Dublin, and School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Nolan
authors.affiliation: Obesity Immunology Group, Education & Research Center, St Vincent's University Hospital, University College Dublin, Dublin, Ireland.|Obesity Immunology Group, National Children's Research Center, Dublin, Ireland.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Hogan
authors.affiliation: Pulmonary and Sleep Disorders Unit, St Vincent's University Hospital, Dublin, and School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: Walter T
authors.initials: WT
authors.lastname: McNicholas
authors.affiliation: Obesity Immunology Group, Education & Research Center, St Vincent's University Hospital, University College Dublin, Dublin, Ireland.
authors.forename: Donal
authors.initials: D
authors.lastname: O'Shea
mesh_terms: D000328:Adult; D017209:Apoptosis; D015687:Cell Hypoxia / Q000276:immunology; D002460:Cell Line; D015897:Comorbidity; D045422:Continuous Positive Airway Pressure; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology*; D009369:Neoplasms / Q000453:epidemiology* / Q000276:immunology / Q000401:mortality; D017286:Polysomnography; D012890:Sleep; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D012913:Snoring / Q000453:epidemiology / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines
keywords: cancer; cytotoxicity; invariant natural killer T cells; obstructive sleep apnea