In-vitro resistance of cloned human glioma cells to natural killer activity of allogeneic peripheral lymphocytes

Abstract

Cells from an established culture of a human astrocytoma were incubated with normal allogeneic peripheral lymphocytes (PBL) in order to study the natural killer (NK) sensitivity of the in vitro propagated cell line. A proportion of cells in culture formed halos, into which lymphocytes did not penetrate. These cells were successfully cloned and showed a decreased susceptibility to NK cytolysis compared with the parent line. Both cell lines could be transplanted into athymic nude mice. The cloned NK-resistant cells underwent a frequent spontaneous regression in nu/nu mice, despite the fact that when used as targets for nu/nu NK cells in vitro they were only moderately susceptible. Phase-contrast microscopy of the mass-cultured cells co-cultivated with lymphocytes suggested that their morphology and ability to form inpenetrable translucent halos might influence their susceptibility to NK lysis. Experiments performed on this assumption revealed that quiescent and halo forming tumour cells were not the primary targets for NK lysis. Cells in mass culture, although tumorigenic, were thus heterogeneous in respect of susceptibility to NK attack. These findings might be relevant to the mechanism of immune escape and tumour heterogeneity in respect of spontaneous cell-mediated lysis.