Interleukin-15 suppresses gastric cancer liver metastases by enhancing natural killer cell activity in a murine model

Interleukin (IL)-15 is a promising cytokine for cancer immunotherapy as it is a critical factor for the proliferation and activation of natural killer (NK) cells. Previous studies have suggested critical roles of IL-15 in tumor invasion and metastasis. However, the association between IL-15 and live...

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Bibliographic Details
Published in:Oncology letters 2018-10, Vol.16 (4), p.4839-4846
Main Authors: Wang, Wei, Jin, Jiejie, Dai, Faxiang, Long, Ziwen, Liu, Xiaowen, Cai, Hong, Zhou, Ye, Chen, Zhong, Huang, Hua
Format: Article
Language:English
Subjects:
Bone marrow
Cancer therapies
Care and treatment
Cytokines
Cytotoxicity
Development and progression
Gastric cancer
Gene expression
Genetic aspects
Health aspects
Immunotherapy
Interleukins
Killer cells
Kinases
Liver
Lymphocytes
Medical prognosis
Metastasis
Mortality
Oncology
Rodents
Spleen
Stomach cancer
Studies
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Summary:Interleukin (IL)-15 is a promising cytokine for cancer immunotherapy as it is a critical factor for the proliferation and activation of natural killer (NK) cells. Previous studies have suggested critical roles of IL-15 in tumor invasion and metastasis. However, the association between IL-15 and liver metastasis of gastric cancer (LMGC) remains unknown. The present study investigated the therapeutic efficacy of recombinant mouse IL-15 (rmIL-15) in murine LMGC models, in which stable green fluorescent protein (GFP)-expressing MKN45 cells (MKN45-GFP cells) were injected into the spleen parenchyma of mice for liver metastasis. At different treatments (high dose group: 2.5 µg of rmIL-15; low dose group: 0.2 µg of rmIL-15; control group: PBS), it was found that rmIL-15 decreased the formation of liver metastasis sites. Additionally, this treatment lead to improved survival of mice following tumor cell transplantation. Treatment with a high dose of rmIL-15 provided greater therapeutic efficacy by prolonged survival of the mice compared with low dose group and control group. It was found that NK cells isolated from the liver that received the high dose of rmIL-15 showed stronger cytotoxic activity compared with the other two groups on the target cells. These findings hold significant importance for the use of IL-15 as a potential adjuvant/therapeutic for liver metastasis from gastric cancer.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2018.9303