title: Altered CD8+ T-Cell Lymphocyte Function and TC1 Cell Stemness Contribute to Enhanced Malignant Tumor Properties in Murine Models of Sleep Apnea.
abstract: The presence of obstructive sleep apnea (OSA) in patients with cancer appears to be accompanied by poorer outcomes. However, the mechanisms underlying such association are unknown. Tumor infiltrating lymphocytes (TILs), including CD8+ T cells, function as cytotoxic T lymphocytes (CTLs) and mount immune responses to cancer by the release of cytolytic enzymes, including granzyme B (GzmB), perforin (Prf), and cytokines such as interferon (IFN)-γ.
  
  
  
  Using established in vivo mouse models, we investigated CD8+ T cells and cancer stem cells (CSCs) in intermittent hypoxia (IH) and sleep fragmentation (SF) in the context of tumor environment.
  
  
  
  Both IH and SF promoted increased tumor growth and invasion toward adjacent tissues compared to controls. The number and frequency of GzmB-producing CD8+ T cells per milligram of tumor tissue was significantly reduced in IH-exposed mice with impaired cytolytic function in both the groups and correlated with tumor weight. We also found that Oct4+ and CD44+CD133+ expressing CSCs were considerably increased in IH and SF tumors, respectively.
  
  
  
  Reductions in GzmB in intratumoral CD8+ T cells in combination with the changes in tumor microenvironment that maintain the ability of CSCs to self-renew and even confer this capability to the nonstem population are compatible with reduced immunosurveillance and adverse tumor outcomes in animal models of OSA.
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Mahzad
authors.initials: M
authors.lastname: Akbarpour
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Zhuanghong
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Alex
authors.initials: A
authors.lastname: Gileles-Hillel
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.|Unitat Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-CIBERES-IDIBAPS, Barcelona, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: Unitat Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-CIBERES-IDIBAPS, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000276:immunology / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009369:Neoplasms; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D047368:Tumor Burden; D059016:Tumor Microenvironment
chemical_list: D015415:Biomarkers; D053804:Granzymes; C509214:Gzmb protein, mouse
keywords: cancer stem cell; cytotoxic T-lymphocytes; granzyme; obstractice sleep apnea.