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Interleukin-15 potentiates human natural killer cells to resist tumor-induced suppression through mTOR-regulated metabolic control
© Lundqvist et al. 2015
Published: 4 November 2015
In cancer patients, anti-tumor functions of NK cells are severely impaired by a variety of immunosuppressive mechanisms. Interleukin (IL)-2 and -15 are two essential cytokines regulating the development and function of human natural killer (NK) cells. Here, we compared the role of IL-2 and IL-15 to render resistance of human NK cells to tumor-induced suppression. We found that early-passage melanoma tumor cells strongly inhibited functions of IL-2 activated NK cells through production of prostaglandin E2 (PGE2). Under the same condition, IL-15 activated NK cells could significantly retain the ability to proliferate in vitro durability, in comparison to IL-2-expanded cells. Altogether, our study uncovers distinct properties between IL-2 and IL-15 on primary human NK cells under tumor-induced suppression. It provides evidence that implementation of IL-15 may greatly improve the clinical efficacy of adoptive NK cell therapy for the treatment of human cancers.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.