Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma.
Aged
Animals
Carcinoma, Hepatocellular
/ therapy
Cell Line, Tumor
Cytokines
/ pharmacology
Disease Models, Animal
Female
Humans
Immunity, Innate
Immunotherapy
/ methods
Interleukin-12
/ pharmacology
Interleukin-15
/ pharmacology
Interleukin-18
/ pharmacology
Killer Cells, Natural
/ physiology
Liver Neoplasms
/ therapy
Male
Mice, Transgenic
NK Cell Lectin-Like Receptor Subfamily K
/ metabolism
Cancer
Cytokines
Immunotherapy
Innate immunity
Liver
Journal
Hepatology international
ISSN: 1936-0541
Titre abrégé: Hepatol Int
Pays: United States
ID NLM: 101304009
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
19
10
2017
accepted:
30
10
2018
pubmed:
24
11
2018
medline:
4
6
2019
entrez:
24
11
2018
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 30467624
doi: 10.1007/s12072-018-9909-3
pii: 10.1007/s12072-018-9909-3
pmc: PMC6513806
doi:
Substances chimiques
Cytokines
0
Interleukin-15
0
Interleukin-18
0
KLRK1 protein, human
0
NK Cell Lectin-Like Receptor Subfamily K
0
Interleukin-12
187348-17-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-83Subventions
Organisme : Medical Research Council
ID : MR/M019829/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C11972/A19917
Pays : United Kingdom
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