Infiltrative and cytolytic activities of lymphokine-activated killer cells against a human glioma spheroid model.
In the present study, we investigated not only the cytotoxic effects of lymphokine-activated killer (LAK) cells on a tumor mass but also the ultrastructural cell-to-cell interaction between LAK effector cells and tumor cells during the cytolytic process within a three-dimensional solid tumor. A multicellular tumor spheroid of a human glioma cell line (U-251MG) was utilized as a solid tumor model. LAK cells were generated from peripheral blood lymphocytes of a healthy donor after stimulation by interleukin 2. Multicellular tumor spheroids with diameters of 500 microns were cocultivated with either LAK cells or nonactivated peripheral blood lymphocytes at the effector:target cell ratio of 20:1, and then time-sequential kinetic, morphological, and ultrastructural analyses were carried out. Morphological and kinetic studies showed that LAK cells directly infiltrated toward the inner areas of multicellular tumor spheroids and caused a progressive tumor destruction. In contrast, peripheral blood lymphocytes hardly exhibited such activities. Ultrastructurally, it was found that the infiltrating LAK effector cells were composed of heterogeneous subpopulations, T-like cells, and large granular lymphocyte-like cells. Both types of lymphocytes tightly adhered to the tumor cells and showed typical morphological features of killing them.
Iwasaki
K
K
Department of Neurosurgery, Kyoto University Medical School, Japan.
Kikuchi
H
H
Miyatake
S
S
Aoki
T
T
Yamasaki
T
T
Oda
Y
Y
D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005910:Glioma / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007700:Kinetics; D008854:Microscopy, Electron; D008954:Models, Biological; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure