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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
16 10 2020
Historique:
received: 18 12 2019
accepted: 24 09 2020
entrez: 17 10 2020
pubmed: 18 10 2020
medline: 18 11 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33067467
doi: 10.1038/s41467-020-19094-0
pii: 10.1038/s41467-020-19094-0
pmc: PMC7568558
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5224

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Auteurs

Christoph Mark (C)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Tina Czerwinski (T)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Susanne Roessner (S)

Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen, Department of Dermatology, Erlangen, Germany.
Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Erlangen, Germany.

Astrid Mainka (A)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Franziska Hörsch (F)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Lucas Heublein (L)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Alexander Winterl (A)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Sebastian Sanokowski (S)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Sebastian Richter (S)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Nina Bauer (N)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany.

Thomas E Angelini (TE)

University of Florida, Department of Mechanical and Aerospace Engineering, Gainesville, FL, USA.

Gerold Schuler (G)

Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen, Department of Dermatology, Erlangen, Germany.
Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Erlangen, Germany.

Ben Fabry (B)

Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Erlangen, Germany. ben.fabry@fau.de.

Caroline J Voskens (CJ)

Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen, Department of Dermatology, Erlangen, Germany.
Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Erlangen, Germany.

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