SUSCEPTIBILITY OF CLONED MELANOMA TO NATURALCYTOTOXICITY

Abstract

This chapter explores the susceptibility of cloned melanoma to natural cytotoxicity. Cell-mediated cytotoxicity against a variety of tumor target cells has been attributed to several effector cell types including activated macrophages, cytotoxic T-lymphocytes, and Fc-receptor bearing null cells. Differences in susceptibility to lysis are not only observed among clonal melanoma subcultures but also within several clones when tested sequentially against the same effector cells. This heterogeneity of the clonal melanoma subcultures with respect to natural killer (NK) lysis may explain the similar but generally less pronounced fluctuations observed in the uncloned culture. The variations in target cell susceptibility to spontaneous lymphocyte-mediated cytotoxicity (SLMC) occurred irrespective of the chromosomal constitution; this suggested that the different melanoma sub-cultures represent clonal evolutions of only one malignant cell clone. As to marker chromosomes, there is no obvious relationship to lysis in SLMC assays. THigh, intermediate, or low susceptibility to NK lysis are relative properties of target cells, which may change with time in culture and can, therefore, influence an objective estimation of effector cell activities. This observation raises particular problems for all clinically oriented SLMC studies involving sequential assays with effector cells from a given donor. The use of a large target cell panel in sequential SLMC assays may circumvent a part of the problems related to the target cell variability.