4.8 Review

Murine models to study human NK cells in human solid tumors

Journal

FRONTIERS IN IMMUNOLOGY
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1209237

Keywords

natural killer cells; humanized mice; solid tumor; human-in-mouse model; tumor immunity

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Since the first studies, mouse models have played a crucial role in understanding NK cells, their development, function, and behavior in normal and tumor tissues. Initially used to study murine NK cells, more sophisticated human-in-mice models have been developed to investigate human NK cells and minimize murine interference. This review provides an overview of the different models used to study NK cells, with a focus on the popular NOG and NSG models, which are used for human-in-mice tumor models, studying transferred human NK cells, and evaluating enhancers of human NK cell function.
Since the first studies, the mouse models have provided crucial support for the most important discoveries on NK cells, on their development, function, and circulation within normal and tumor tissues. Murine tumor models were initially set to study murine NK cells, then, ever more sophisticated human-in-mice models have been developed to investigate the behavior of human NK cells and minimize the interferences from the murine environment. This review presents an overview of the models that have been used along time to study NK cells, focusing on the most popular NOG and NSG models, which work as recipients for the preparation of human-in-mice tumor models, the study of transferred human NK cells, and the evaluation of various enhancers of human NK cell function, including cytokines and chimeric molecules. Finally, an overview of the next generation humanized mice is also provided along with a discussion on how traditional and innovative in-vivo and in-vitro approaches could be integrated to optimize effective pre-clinical studies.

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