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Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
Cryopreservation impairs 3-D migration and cytotoxicity of natural killer cells
Christoph Mark1, Tina Czerwinski1, Susanne Roessner2,3,4
1Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.
Abstract:
Natural killer (NK) cells are important effector cells in the immune response to cancer. Clinical trials on adoptively transferred NK cells in patients with solid tumors, however, have thus far been unsuccessful. As NK cells need to pass stringent safety evaluation tests before clinical use, the cells are cryopreserved to bridge the necessary evaluation time. Standard degranulation and chromium release cytotoxicity assays confirm the ability of cryopreserved NK cells to kill target cells. Here, we report that tumor cells embedded in a 3-dimensional collagen gel, however, are killed by cryopreserved NK cells at a 5.6-fold lower rate compared to fresh NK cells. This difference is mainly caused by a 6-fold decrease in the fraction of motile NK cells after cryopreservation. These findings may explain the persistent failure of NK cell therapy in patients with solid tumors and highlight the crucial role of a 3-D environment for testing NK cell function.
Insights
Cryopreserved natural killer (NK) cells show reduced tumor-killing ability in 3D environments due to decreased motility. This finding may explain the failure of NK cell therapy in solid tumors.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Natural killer (NK) cells are crucial immune effectors against cancer.
- Adoptive NK cell therapy for solid tumors has faced challenges.
- Cryopreservation is necessary for NK cell safety evaluations before clinical use.
Purpose of the Study:
- To investigate the efficacy of cryopreserved NK cells against tumor cells in a 3D environment.
- To identify factors contributing to the limited success of NK cell therapy in solid tumors.
Main Methods:
- Comparison of cryopreserved and fresh NK cell cytotoxicity against 3D-embedded tumor cells.
- Assessment of NK cell motility in a 3D collagen gel model.
Main Results:
- Cryopreserved NK cells exhibited a 5.6-fold lower killing rate of 3D-embedded tumor cells compared to fresh NK cells.
- A significant 6-fold decrease in NK cell motility was observed after cryopreservation.
- Reduced NK cell motility in 3D environments is a key factor in diminished anti-tumor activity.
Conclusions:
- The 3D microenvironment is critical for accurately assessing NK cell function.
- Impaired NK cell motility post-cryopreservation contributes to therapeutic failures in solid tumors.
- Future strategies should consider NK cell motility and 3D tumor architecture for effective immunotherapy.
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