Dynamic Analysis of Human Natural Killer Cell Response at Single-Cell Resolution in B-Cell Non-Hodgkin Lymphoma

Frontiers in Immunology
S SarkarT Konry

Abstract

Natural killer (NK) cells are phenotypically and functionally diverse lymphocytes that recognize and kill cancer cells. The susceptibility of target cancer cells to NK cell-mediated cytotoxicity depends on the strength and balance of regulatory (activating/inhibitory) ligands expressed on target cell surface. We performed gene expression arrays to determine patterns of NK cell ligands associated with B-cell non-Hodgkin lymphoma (b-NHL). Microarray analyses revealed significant upregulation of a multitude of NK-activating and costimulatory ligands across varied b-NHL cell lines and primary lymphoma cells, including ULBP1, CD72, CD48, and SLAMF6. To correlate genetic signatures with functional anti-lymphoma activity, we developed a dynamic and quantitative cytotoxicity assay in an integrated microfluidic droplet generation and docking array. Individual NK cells and target lymphoma cells were co-encapsulated in picoliter-volume droplets to facilitate monitoring of transient cellular interactions and NK cell effector outcomes at single-cell level. We identified significant variability in NK-lymphoma cell contact duration, frequency, and subsequent cytolysis. Death of lymphoma cells undergoing single contact with NK cells occurred f...Continue Reading

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Citations

Nov 7, 2018·Lab on a Chip·Aude I SegalinyWeian Zhao
Jun 8, 2019·SLAS Technology·Mosfera A ChowduryEdmond W K Young
Nov 22, 2019·Scientific Reports·Afshin BeheshtiAndrew M Evens
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Feb 9, 2021·Advanced Science·Benjamin A YangCarlos A Aguilar
May 13, 2021·Experimental Hematology·Ignacio Campillo-MarcosManel Esteller

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Datasets Mentioned

BETA
GSE102930

Methods Mentioned

BETA
flow cytometry
chips
ELISA

Software Mentioned

R
ImageJ
Office Excel
Zen
Origin Pro

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