title: Association of decreased NK cell activity and IFNγ expression with pSTAT dysregulation in breast cancer patients.
abstract: OBJECTIVE
  Impaired IFNγ production in peripheral blood lymphocytes (PBL) and their subsets reflects immunosuppression and inadequate antitumor immune response in cancer patients. Decreased function of natural killer (NK) cells has not been investigated in breast cancer with respect to altered pSTAT signaling pathways.
  
  
  METHODS
  PBL of breast cancer patients and healthy controls were analyzed for IFNγ and pSTAT1 expression and NK cell activity using flow cytometry and (51)Cr-release assay, respectively. The level of pSTAT1, 3 and 5 was investigated by Western blotting.
  
  
  RESULTS
  Our results indicated that PBL and CD3(-) CD16(+) NK cells of patients had significantly lower level of IFNγ. The patients had a significantly decreased NK cell cytotoxicity compared to controls, with the decrease being dependent on the stage of disease. Positive correlation between IFNγ level in PBL and NK cytotoxicity in controls and patients was also shown. The PBL of patients, compared to controls, expressed lower level of pSTAT1, 3 and 5. The patients' T and NK cell subsets had lower pSTAT1 level.
  
  
  CONCLUSIONS
  This study indicates that pSTAT1 in PBL of breast cancer patients could be a biomarker of decreased NK cell cytotoxicity and IFNγlevel that are associated with progression of this disease.
authors.affiliation: Institute of Oncology and Radiology of Serbia, Department of Experimental Oncology, Belgrade, Serbia. konjevicg@ncrc.ac.rs
authors.forename: G
authors.initials: G
authors.lastname: Konjevic
authors.forename: S
authors.initials: S
authors.lastname: Radenkovic
authors.forename: T
authors.initials: T
authors.lastname: Srdic
authors.forename: V
authors.initials: V
authors.lastname: Jurisic
authors.forename: Lj
authors.initials: Lj
authors.lastname: Stamatovic
authors.forename: M
authors.initials: M
authors.lastname: Milovic
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000097:blood / Q000276:immunology / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000276:immunology* / Q000556:secondary; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology / Q000556:secondary; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology / Q000556:secondary; D008207:Lymphatic Metastasis; D008214:Lymphocytes; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000097:blood*; D015398:Signal Transduction
chemical_list: D050791:STAT Transcription Factors; D007371:Interferon-gamma