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Morphologic analysis of human lymphokine-activated killer (LAK) cells
P Groscurth1, S Diener, R Stahel
1Institute of Anatomy, University of Zürich, Switzerland.
International Journal of Cancer
|April 15, 1990
Summary
Lymphokine-activated killer (LAK) cells exhibit distinct ultrastructure and effectively destroy tumor cells via mechanisms similar to cytotoxic T-lymphocytes and NK cells, confirmed by advanced microscopy and molecular assays.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Lymphokine-activated killer (LAK) cells are crucial in adoptive immunotherapy.
- Understanding LAK cell ultrastructure and cytotoxic mechanisms is vital for optimizing cancer treatment.
Purpose of the Study:
- To characterize the ultrastructure of LAK cells during in vitro cultivation.
- To investigate the cytotoxic mechanisms of LAK cells against tumor targets.
- To compare LAK cell characteristics with cytotoxic T-lymphocytes (CTL) and NK cells.
Main Methods:
- Scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
- Immuno-electron microscopy for perforin I localization.
- In situ hybridization for mRNA detection (perforin I, granzyme A).
- Flow cytometry for DNA content analysis.
- 51Cr-release assay for cytotoxic activity assessment.
Main Results:
- LAK cells showed uniform ultrastructure with specific lysosomal granules containing perforin I.
- Perforin I and granzyme A mRNA were detected in LAK cell cytoplasm.
- Nuclear inclusion bodies were observed but not associated with aneuploidy.
- LAK cells effectively lysed K562 and DAUDI tumor cells.
- Tumor cell membrane damage was the initial LAK cell attack site.
Conclusions:
- LAK cells possess a unique ultrastructure distinct from CTL and NK cells.
- LAK cells employ mechanisms similar to other cytotoxic effector cells to destroy tumor cells.
- These findings enhance the understanding of LAK cell-mediated tumor cell lysis.