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-N KG2a 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.