Single-Cell Profiling Reveals Functional Heterogeneity and Serial Killing in Human Peripheral and Ex Vivo-Generated CD34+ Progenitor-Derived Natural Killer Cells

Nikita Subedi, Liesbeth Petronella Verhagen, Paul de Jonge, Laura C. Van Eyndhoven, Mark C. van Turnhout, Vera Koomen, Jean Baudry, Klaus Eyer, Harry Dolstra, Jurjen Tel (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Increasing evidence suggests that natural killer (NK) cells are composed of distinct functional subsets. This multifunctional role has made them an attractive choice for anticancer immunotherapy. A functional NK cell repertoire is generated through cellular education, resulting in a heterogeneous NK cell population with distinct capabilities responding to different stimuli. The application of a high-throughput droplet-based microfluidic platform allows monitoring of NK cell-target cell interactions at the single-cell level and in real-time. A variable response of single NK cells toward different target cells is observed, and a distinct population of NK cells (serial killers) capable of inducing multiple target lysis is identified. By assessing the cytotoxic dynamics, it is shown that single umbilical cord blood-derived CD34+ hematopoietic progenitor (HPC)-NK cells display superior antitumor cytotoxicity. With an integrated analysis of cytotoxicity and cytokine secretion, it is shown that target cell interactions augment cytotoxic as well as secretory behavior of NK cells. By providing an integrated assessment of NK cell functions by microfluidics, this study paves the way to further functionally characterize NK cells ultimately aimed to improve cancer immunotherapy.

Original languageEnglish
Article number2200207
Number of pages12
JournalAdvanced Biology
Volume7
Issue number4
DOIs
Publication statusPublished - Apr 2023

Bibliographical note

Funding Information:
These results are part of the project that has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant Agreement No. 802791). Furthermore, the authors acknowledge the generous support from the Eindhoven University of Technology.

Funding

These results are part of the project that has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant Agreement No. 802791). Furthermore, the authors acknowledge the generous support from the Eindhoven University of Technology.

Keywords

  • droplet-based microfluidics
  • effector functions
  • functional heterogeneity
  • natural killer cells
  • NK cell-based immunotherapy
  • single cell studies
  • Antigens, CD34
  • Killer Cells, Natural
  • Humans
  • Cells, Cultured
  • Cell Differentiation
  • Cytotoxicity, Immunologic

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