Single-cell analysis reveals functional heterogeneity and serial killing of human peripheral and ex vivo generated CD34+ progenitor-derived natural killer cells (2023)

Abstract

Accumulating evidence indicates that natural killer (NK) cells consist of distinct functional subsets. This multifunctional role makes them an attractive option for anticancer immunotherapy. Functional NK cell repertoires are generated through cell formation, resulting in heterogeneous NK cell populations with varying abilities to respond to different stimuli. The application of a droplet-based high-throughput microfluidic platform enables real-time monitoring of NK cell-target cell interactions at the single-cell level. Different responses of individual NK cells to different target cells were observed and distinct NK cell populations (serial killers) capable of inducing lysis of multiple target cells were identified. Single umbilical cord blood-derived CD34+ hematopoietic progenitor (HPC) NK cells showed excellent antitumor cytotoxicity by evaluating cytotoxicity kinetics. Through comprehensive analysis of cytotoxicity and cytokine secretion, it was shown that target cell interaction enhances the cytotoxic and secretory behavior of NK cells. With comprehensive assessment of NK cell function via microfluidics, this study paves the way for further functional characterization of NK cells with the aim of improving cancer immunotherapy.

original languageEnglish
Item Number2200207
page number12
journalAdvanced Biology
volume7
issue number4
two
Post statuspost-April 2023

bibliographic notes

Financing Information:
These results are part of a project funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement number 802791). In addition, the authors thank the Eindhoven University of Technology for their generous support.

Key words

  • Droplet-Based Microfluidics
  • effect function
  • functional heterogeneity
  • natural killer cells
  • NK cell-based immunotherapy
  • single cell research

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    Subedi, N., Verhagen, L.P., DeJonger, P., Van Eyndhoven, L.C., van Turnhout, M.C., Koomen , V. , Baudry , J. , Eyer , K. , Dolstra , H. ( 2008 ).(2023)。Single-cell analysis reveals functional heterogeneity and serial killing of human peripheral and ex vivo generated CD34+ progenitor-derived natural killer cells.Advanced Biology,7(4), [2200207]。https://doi.org/10.1002/adbi.202200207

    Subedi, Nikita; Verhagen,Liesbeth Petronella; De Junger, Paul et al. /Single-cell analysis reveals functional heterogeneity and serial killing of human peripheral and ex vivo generated CD34+ progenitor-derived natural killer cells.exist:Advanced Biology. 2023; flight. 7, 4th.

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    title = "Single-cell analysis reveals functional heterogeneity and serial killing of human peripherally and ex vivo generated CD34+ progenitor-derived natural killer cells",

    Abstract = "Increasing evidence indicates that natural killer (NK) cells are composed of distinct functional subpopulations. This multifunctional role makes them an attractive option for anticancer immunotherapy. Functional NK cell repertoires are developed through Cell formation results in heterogeneous NK cell populations with different abilities to respond to different stimuli. The application of a droplet-based high-throughput microfluidic platform enables real-time monitoring of NK cell-target cell interactions at the single-cell level. Observation to the differential response of individual NK cells to different target cells, and identified distinct NK cell populations (serial killers) capable of inducing lysis of multiple target cells. By assessing cytotoxicity kinetics, it was shown that single cord blood-derived CD34+ hematopoietic progenitor cells ( HPC)-NK cells exhibited excellent anti-tumor cytotoxicity. Comprehensive analysis of cytotoxicity and cytokine secretion indicated that target cell interaction enhanced the cytotoxicity and secretion behavior of NK cells. NK cell function was investigated by microfluidics Taken together, this study paves the way for further functional characterization of NK cells, ultimately aimed at improving cancer immunotherapy."

    Keywords = "droplet-based microfluidics, effector function, functional heterogeneity, natural killer cells, NK cell-based immunotherapy, single-cell research",

    Authors = "Nikita Subedi and Verhagen, {Liesbeth Petronella} and {de Jonge}, Paul and {Van Eyndhoven}, {Laura C.} and {van Turnhout}, {Mark C.} and Vera Koomen, Jean Baudry and Klaus Eyer and Harry Dostra and Uergen Tell",

    note = "Funding information: These results are part of a project funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (funding agreement number 802791). In addition, the authors thank their Eindhoven University of Technology for their generosity support.",

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    Subedi, N, Verhagen, L.P, DeJonger, P, Van Eindhoven, LC, van Turnhout, MC, Koomen , V , Baudry , J , Eyer , K , Dolstra , H2023, 'Single-cell analysis reveals functional heterogeneity and serial killing of human peripheral and ex vivo generated CD34+ progenitor-derived natural killer cells',Advanced Biology, flight. 7. No. 4. 2200207.https://doi.org/10.1002/adbi.202200207

    Single-cell analysis reveals functional heterogeneity and serial killing of human peripheral and ex vivo generated CD34+ progenitor-derived natural killer cells/ Subedi, Nikita; Verhagen,Liesbeth Petronella; De Junger, Paul et al.
    exist:Advanced Biology, flight. 7, No. 4, 2200207, 04.2023.

    Research results:Contributions to JournalsarticleAcademicpeer review

    you-label

    T1-single-cell analysis reveals functional heterogeneity and serial killing of human peripherally and ex vivo generated CD34+ progenitor-derived natural killer cells

    AU——Subedi, Nikita

    AU – Verhagen, Liesbeth Petronella

    AU – de Jonge, Paul

    AU - Van Eyndhoven、Laura C.

    AU van Turnhout, Mark C.

    AU – Koomen, Vera

    AU – Baudry, Jean

    AU-Eyer, Klaus

    AU - Dolstra, Harry

    On the phone. jurjen

    N1 - Funding information: These results are part of a project funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement number 802791). In addition, the authors thank the Eindhoven University of Technology for their generous support.

    Financial Year - 2023/4

    First Year – 2023/4

    N2 - Accumulating evidence indicates that natural killer (NK) cells consist of distinct functional subsets. This multifunctional role makes them an attractive option for anticancer immunotherapy. Functional NK cell repertoires are generated through cell formation, resulting in heterogeneous NK cell populations with varying abilities to respond to different stimuli. The application of a droplet-based high-throughput microfluidic platform enables real-time monitoring of NK cell-target cell interactions at the single-cell level. Different responses of individual NK cells to different target cells were observed and distinct NK cell populations (serial killers) capable of inducing lysis of multiple target cells were identified. Single umbilical cord blood-derived CD34+ hematopoietic progenitor (HPC) NK cells showed excellent antitumor cytotoxicity by evaluating cytotoxicity kinetics. Through comprehensive analysis of cytotoxicity and cytokine secretion, it was shown that target cell interaction enhances the cytotoxic and secretory behavior of NK cells. With comprehensive assessment of NK cell function via microfluidics, this study paves the way for further functional characterization of NK cells with the aim of improving cancer immunotherapy.

    AB - Accumulating evidence indicates that natural killer (NK) cells are composed of distinct functional subsets. This multifunctional role makes them an attractive option for anticancer immunotherapy. Functional NK cell repertoires are generated through cell formation, resulting in heterogeneous NK cell populations with varying abilities to respond to different stimuli. The application of a droplet-based high-throughput microfluidic platform enables real-time monitoring of NK cell-target cell interactions at the single-cell level. Different responses of individual NK cells to different target cells were observed and distinct NK cell populations (serial killers) capable of inducing lysis of multiple target cells were identified. Single umbilical cord blood-derived CD34+ hematopoietic progenitor (HPC) NK cells showed excellent antitumor cytotoxicity by evaluating cytotoxicity kinetics. Through comprehensive analysis of cytotoxicity and cytokine secretion, it was shown that target cell interaction enhances the cytotoxic and secretory behavior of NK cells. With comprehensive assessment of NK cell function via microfluidics, this study paves the way for further functional characterization of NK cells with the aim of improving cancer immunotherapy.

    KW - Droplet-Based Microfluidics

    KW – effect function

    KW - functional heterogeneity

    KW - natural killer cells

    KW - NK Cell Based Immunotherapy

    KW - Single Cell Research

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    DO – 10.1002/adbi.202200207

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    Serial Number - 2701-0198

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    Subedi N, Record company, young P, Van Eindhoven LC, van Turnhout MC, Koomen V et al.Single-cell analysis reveals functional heterogeneity and serial killing of human peripheral and ex vivo generated CD34+ progenitor-derived natural killer cells.Advanced Biology. 2023 Apr;7(4):2200207. doi: 10.1002/adbi.202200207

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