title: Expansion of natural killer cells in patients with head and neck cancer: detection of "noninhibitory" (activating) killer Ig-like receptors on circulating natural killer cells.
abstract: BACKGROUND
  In a group of patients with head and neck cancers (H&NC), the expansion of the population of CD3-,CD16+ natural killer (NK) cells in the peripheral blood was studied.
  
  
  METHODS
  Cytofluorimetric analysis of the expression of killer Ig-like receptors (KIR, namely p58.1, p58.2, p58.3, p70, and p140) and CD94-NKG2a was performed. Cytolytic activities were studied using 51Cr release assay. T and NK cell cloning was performed using limiting dilution culture conditions. Cytokine production was analyzed using commercial enzyme immunoassays.
  
  
  RESULTS
  Phenotypic analysis showed that the expanded populations were heterogeneous. Even in the presence of a large number of circulating NK cells, "nonspecific" cytolytic capacities were heavily reduced, whereas cytolytic capacity related to T cells was virtually normal. Unlike NK cell clones derived from healthy donors, most NK cells derived from H&NC patients expressed surface "activating" NK cell receptors (KAR) for HLA, detected by use of a redirected cytolytic assay. Analysis of the CD4+ subpopulation at the clonal level demonstrated that they had a severe proliferative defect.
  
  
  CONCLUSIONS
  These experimental data indicated that H&NC patients have a polyclonal expansion of functionally deficient NK cells expressing KAR. In addition, the proliferative capacity of patients' "helper" cells was strongly inhibited, thus accounting for a severe impairment of cytolytic activity of the expanded NK cells.
authors.affiliation: Laboratorio di Immunoterapia Cellulare, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10, 16132 Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Melioli
authors.forename: Claudia
authors.initials: C
authors.lastname: Semino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Margarino
authors.forename: Paola
authors.initials: P
authors.lastname: Mereu
authors.forename: Marco
authors.initials: M
authors.lastname: Scala
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cangemi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Crocetti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Machì
authors.forename: Guido
authors.initials: G
authors.lastname: Ferlazzo
mesh_terms: D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D010641:Phenotype; D011971:Receptors, Immunologic / Q000097:blood* / Q000235:genetics; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D013997:Time Factors
chemical_list: C515078:KIR2DL3 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; C098698:p70 natural killer cell receptor