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.
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.
Melioli
Giovanni
G
Laboratorio di Immunoterapia Cellulare, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10, 16132 Genoa, Italy.
Semino
Claudia
C
Margarino
Giovanni
G
Mereu
Paola
P
Scala
Marco
M
Cangemi
Giuliana
G
Crocetti
Emanuele
E
Machì
Anna Maria
AM
Ferlazzo
Guido
G
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
C515078:KIR2DL3 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; C098698:p70 natural killer cell receptor