Damage to multicellular human H-2 glioma spheroids incubated with LAK cells: an ultrastructural study.

Local brain tumor therapy using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) has not proved to be effective in preliminary clinical trials. One obstacle to effective use of this therapy is ignorance about the events that follow contact of the LAK cells with glioma tissue. We used multicellular spheroids grown from human glioma cell lines as targets to study, in vitro, the effect of LAK cells against three-dimensional glioma tissue. Here we describe the ultrastructural changes in spheroids of H-2 glioma cells incubated in pellets of LAK cells for up to 24 hours. In H-2 spheroids, cellular damage was not restricted to the effector cell-target cell (effector-target) contact; it extended farther, at least partly because of nonspecific changes in the spheroid micromilieu. Formation of cytoplasmic blebs, a characteristic effect of T cells, natural killer cells, and LAK cells on single target cells, also occurs in H-2 spheroids, and it is not limited to the effector-target contact area either. These findings suggest that LAK cells release membrane-damaging agents that remain active outside the effector-target area, in the micromilieu of H-2 spheroid tissue.