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.
Conclusion:
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.