Defective natural cytotoxicity in patients with cancer: normal number of effector cells but decreased recycling capacity in patients with advanced disease.

Abstract

Patients with advanced cancer exhibited lower natural cytotoxicity against K562 target cells in a standard short-term chromium release assay than did patients with localized malignancy or normal individuals. Although natural killer (NK) activity of advanced cancer patients could be augmented by nylon column depletion of adherent cells and enriched further by fractionation of discontinuous Percoll gradients, the NK level attained remained below that obtained from PBL of normal donors treated by the same procedures. The pattern of NK activity obtained on the Percoll gradients was the same for all individuals studied. The proportion of large granular lymphocytes (LGL) paralleled NK activity and was highest in the peak NK fraction in all individuals tested. Advanced cancer patients with low NK activity showed no decrease in number of LGL from that of other cancer patients or normals. Similarly, there was no decrease in target binding cell number. Using a single-cell assay in agarose, we found that the number of active NK cells was the same for all patients, whether with localized or advanced malignancy, and normal subjects. In a 3-hr time period, there were no differences in the rate of killing in agarose. The maximum killing potential (Vmax) of the NK-deficient advanced cancer patients in a 51Cr-release assay was significantly lower than that of normals or other cancer patients. The observed defect in natural cytotoxicity of these patients thus appeared to be due to a reduced recycling capacity.