Lysis of fresh human B-lymphocyte-derived leukemia cells by interferon-activated natural killer (NK) cells

Abstract

Fresh neoplastic B cells from 14 untreated patients with naturally occurring B-cell leukemias were found to be susceptible to lysis by human natural killer (NK) cells. The observed lysis of the fresh, non-cultured, neoplastic B cells was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK target K562. A further finding was the correlation of NK susceptibility with disease activity in 11 patients with chronic lymphocytic (CLL) and one patient with lymphosarcoma cell leukemia (LSCL). Enriched neoplastic B cells from seven untreated patients with non-progressive CLL, whose disease activity was stable throughout the 6 month period of study, exhibited persistent and essentially unchanged NK susceptibility profiles. In contrast, four untreated patients with progressive CLL also had a measurable fraction of NK-susceptible, neoplastic targets, but these cells subsequently disappeared after successful cytoreductive therapy, and later re-emerged when these patients again developed progressive disease. Furthermore, one patient with LSCL was found to have persistent, measurable NK susceptibility in his tumor-enriched fraction after unsuccessful cytoreductive therapy. An additional finding in the peripheral blood of patients with chronic B-cell leukemias was the presence of significantly lower NK effector-cell activity against K562 as compared to normal donor peripheral blood lymphocytes (PBLs). The implications of these findings are discussed.