Cryopreservation impairs 3-D migration and cytotoxicity of natural killer cells

Christoph Mark, Tina Czerwinski, Susanne Roessner, Astrid Mainka, Franziska Hörsch, Lucas Heublein, Alexander Winterl, Sebastian Sanokowski, Sebastian Richter, Nina Bauer, Thomas E. Angelini, Gerold Schuler, Ben Fabry () and Caroline J. Voskens
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Christoph Mark: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Tina Czerwinski: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Susanne Roessner: Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen, Department of Dermatology
Astrid Mainka: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Franziska Hörsch: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Lucas Heublein: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Alexander Winterl: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Sebastian Sanokowski: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Sebastian Richter: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Nina Bauer: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Thomas E. Angelini: University of Florida, Department of Mechanical and Aerospace Engineering
Gerold Schuler: Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen, Department of Dermatology
Ben Fabry: Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics
Caroline J. Voskens: Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen, Department of Dermatology

Nature Communications, 2020, vol. 11, issue 1, 1-8

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19094-0

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