INFILTRATION AND LYSIS OF TUMOR-CELL AGGREGATES BY ADHERENT INTERLEUKIN-2-ACTIVATED NATURAL-KILLER-CELLS IS DISTINCT FROM SPECIFIC CYTOLYSIS

Adoptively transferred activated natural killer (A-NK) cells infiltrat e tumours in vivo. Two in vitro B16-F10 melanoma tumour models were us ed to study with fluorescence and electron microscopy the infiltration of adherent interleukin 2 (IL-2) A-NK cells: (1) substratum-bound ses sile microtumours (MTs), and (2) three-dimensional cell growth on macr oporous gelatinous microcarriers (Cultispheres(R)). From 2 h and on in creasing numbers of A-NK cells infiltrated the MTs regularly surrounde d by a widened intercellular space. An IL-2-dependent disintegration o f MTs began at 6-8 h resulting in a release of vital and dead cells. A -NK cell invasion into Cultispheres effectively displaced the melanoma cells from the highly convoluted substratum. Thus, A-NK cell infiltra tion had a protease-like effect on the tumour cell aggregates which mi ght have a bearing on the interpretation of their cytolytic effect on target cells. Ultrastructural evidence was not obtained of specific A- NK/target conjugate formation or of granule-mediated target cell destr uction in either model tumor.