Natural Killer Cell Activity and Autologous Tumor Killing Activity in Cancer Patients: Overlapping Involvement of Effector Cells as Determined in Two-Target Conjugate Cytotoxicity Assay2

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Abstract
The relationship between natural killer (NK) cell activity and autologous tumor killing activity was examined in patients with carcinomatous pleural effusions (PE) by means of a two-target conjugate cytotoxicity assay. Enrichment of large granular Iymphocyte(s) (LGL) by discontinuous Percoll gradient centrifugation resulted in an augmentation of cytotoxicity against both K562 cells and tumor cells freshly isolated from PE of the same patients in a 4-hour 51Cr release cytotoxicity assay. At the single-cell level, the LGL-enriched fraction contained an increased number of effector cells that bound to autologous tumor cells and to K562 cells, as well as an increased frequency of cells cytotoxic to these target cells. In the two-target conjugate cytotoxicity assay, a single lymphocyte in the LGL population simultaneously bound to both a fluorescein-labeled K562 cell and a nonfluorescent autologous tumor cell. A significant number of lymphocytes in these mixed two-target conjugates lysed both autologous tumor cells and K562 cells after 6 hours' incubation, although overall lysis of K562 cells was higher than that of autologous tumor cells. These results indicate that a single LGL is involved in the lysis of both autologous tumor cells and K562 cells and thus provide direct evidence of involvement of subsets of NK cells in autologous tumor cell killing.