The University of Southampton
University of Southampton Institutional Repository

Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma

Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma
Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is common, but remains difficult to treat. Natural killer (NK) cells are cells of the innate immune system that have potent anti-cancer activity. Recent work has shown that stimulation with IL-12/15/18 leads to the generation of NK cells with enhanced functional and putative “memory” properties. We have investigated the activity of these NK cells against HCC cell lines in vitro and in a mouse model. Methods: NK cells from healthy donors or individuals with HCC were activated with IL-12/15/18 in vitro and tested for cytotoxic activity against a panel of human HCC cell lines. IL-12/15/18 primed murine NK cells were then infused into a murine model of spontaneously arising HCC to test for anti-tumor activity. Results: NK cells from patients and healthy controls had similar expression levels of activating and inhibitory NK cell receptors. However, proliferation of NK cells from HCC patients was weaker than healthy controls in response to IL-12/15/18 and IL-2 (p < 0.001 at day 9). In vitro, NK cells from both groups of individuals killed HCC targets to similar levels and this was unrelated to NKG2D expression. In a spontaneous model of HCC, IL-12/15/18 activated NK cells trafficked to the liver and resulted in lower levels of spontaneous HCC formation (p < 0.01). Conclusion: Cytokine-primed NK cells from patients with HCC have similar levels of activity against HCC cell lines as those from healthy controls. This type of activated NK cell has immunotherapeutic potential against hepatocellular carcinoma.

Cancer, Cytokines, Immunotherapy, Innate immunity, Liver
1936-0533
1-9
Zhuang, Lihui
9c3ed588-5c92-407c-b3ba-8b2c7e26f143
Fulton, Rebecca J.
848aa9dc-797f-40f8-b63d-bca0d90f7b55
Rettman, Pauline
d761e696-6680-4168-931d-4586a6062a58
Sayan, A. Emre
5590c6d1-6562-46be-a002-98adc087f1b6
Coad, Jonathan
37e53b9b-c1ae-4623-9d45-ce7e4b9a5125
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Zhuang, Lihui
9c3ed588-5c92-407c-b3ba-8b2c7e26f143
Fulton, Rebecca J.
848aa9dc-797f-40f8-b63d-bca0d90f7b55
Rettman, Pauline
d761e696-6680-4168-931d-4586a6062a58
Sayan, A. Emre
5590c6d1-6562-46be-a002-98adc087f1b6
Coad, Jonathan
37e53b9b-c1ae-4623-9d45-ce7e4b9a5125
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Zhuang, Lihui, Fulton, Rebecca J., Rettman, Pauline, Sayan, A. Emre, Coad, Jonathan, Al-Shamkhani, Aymen and Khakoo, Salim I. (2018) Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma. Hepatology International, 1-9. (doi:10.1007/s12072-018-9909-3).

Record type: Article

Abstract

Background: Hepatocellular carcinoma (HCC) is common, but remains difficult to treat. Natural killer (NK) cells are cells of the innate immune system that have potent anti-cancer activity. Recent work has shown that stimulation with IL-12/15/18 leads to the generation of NK cells with enhanced functional and putative “memory” properties. We have investigated the activity of these NK cells against HCC cell lines in vitro and in a mouse model. Methods: NK cells from healthy donors or individuals with HCC were activated with IL-12/15/18 in vitro and tested for cytotoxic activity against a panel of human HCC cell lines. IL-12/15/18 primed murine NK cells were then infused into a murine model of spontaneously arising HCC to test for anti-tumor activity. Results: NK cells from patients and healthy controls had similar expression levels of activating and inhibitory NK cell receptors. However, proliferation of NK cells from HCC patients was weaker than healthy controls in response to IL-12/15/18 and IL-2 (p < 0.001 at day 9). In vitro, NK cells from both groups of individuals killed HCC targets to similar levels and this was unrelated to NKG2D expression. In a spontaneous model of HCC, IL-12/15/18 activated NK cells trafficked to the liver and resulted in lower levels of spontaneous HCC formation (p < 0.01). Conclusion: Cytokine-primed NK cells from patients with HCC have similar levels of activity against HCC cell lines as those from healthy controls. This type of activated NK cell has immunotherapeutic potential against hepatocellular carcinoma.

Text
Zhuang 2018 Article Activity OfIL-121518 Primed Natur - Version of Record
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 30 October 2018
e-pub ahead of print date: 22 November 2018
Keywords: Cancer, Cytokines, Immunotherapy, Innate immunity, Liver

Identifiers

Local EPrints ID: 426638
URI: https://eprints.soton.ac.uk/id/eprint/426638
ISSN: 1936-0533
PURE UUID: f70e6f90-57be-44a4-8d51-31749f4ead3e
ORCID for Aymen Al-Shamkhani: ORCID iD orcid.org/0000-0003-0727-4189

Catalogue record

Date deposited: 07 Dec 2018 17:30
Last modified: 14 Mar 2019 01:49

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×