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Int J Biol Sci 2018; 14(3):331-340. doi:10.7150/ijbs.22809 This issue Cite

Research Paper

Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy

Hiroaki Senju1,2,3, Asuka Kumagai2, Yoichi Nakamura1,3, Hiroyuki Yamaguchi1,3, Katsumi Nakatomi1,3, Shota Fukami2, Kengo Shiraishi2, Yuka Harada2, Mitsuhiro Nakamura2, Haruki Okamura4, Yoshimasa Tanaka2,4✉, Hiroshi Mukae1,3

1. Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
2. Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
3. Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
4. Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan

✉ Corresponding author: ystanakaac.jp, phone number: (81)-958198522

Citation:
Senju H, Kumagai A, Nakamura Y, Yamaguchi H, Nakatomi K, Fukami S, Shiraishi K, Harada Y, Nakamura M, Okamura H, Tanaka Y, Mukae H. Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy. Int J Biol Sci 2018; 14(3):331-340. doi:10.7150/ijbs.22809. https://www.ijbs.com/v14p0331.htm
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Abstract

Graphic abstract

When pathogenic stresses are recognized by innate immune cells, inflammasomes are assembled and caspase-1 is activated, resulting in the conversion of pro-IL-18 into mature IL-18. Because natural killer (NK) cells express IL-18 receptors, IL-18 may play roles in immune functions of NK cells. In the present study, we examined the effect of IL-18 on NK cells derived from lung cancer patients and healthy adult volunteers. When peripheral blood NK cells were stimulated with IL-2, the cells formed clusters beginning on day 5-6 and proliferated thereafter, in which the number of NK cells increased by 10-fold in 10 days. When IL-18 was added, cell clusters were observed as early as on day 4 and NK cells proliferated vigorously. On day 10, the expansion rate was 56-fold on average, showing that IL-18 promoted the expansion of NK cells. It was also notable that IL-18 enhanced the expression of CD80, CD86, HLA-DR and HLA-DQ on NK cells, suggesting that IL-18 conferred NK cells an APC-like phenotype. When cellular cytotoxicity was determined, APC-like NK cells efficiently killed tumor cells and anti-tumor activity was augmented by the addition of tumor antigen-specific mAbs. In addition, IFN-γ was produced by APC-like NK cells in response to tumor cells, and the cytokine production was further enhanced by mAbs. Taken together, IL-18 not only promoted the expansion of NK cells, but also changed the phenotype of NK cells. IL-2/IL-18-induced NK cells might, therefore, serve as a bridge between innate immunity and adaptive immunity and be useful for cancer immunotherapy.

Keywords: IL-18, NK cells, antigen-presenting cells, PD-1, immune checkpoint

Citation styles

APA
Senju, H., Kumagai, A., Nakamura, Y., Yamaguchi, H., Nakatomi, K., Fukami, S., Shiraishi, K., Harada, Y., Nakamura, M., Okamura, H., Tanaka, Y., Mukae, H. (2018). Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy. International Journal of Biological Sciences, 14(3), 331-340. https://doi.org/10.7150/ijbs.22809.

ACS
Senju, H.; Kumagai, A.; Nakamura, Y.; Yamaguchi, H.; Nakatomi, K.; Fukami, S.; Shiraishi, K.; Harada, Y.; Nakamura, M.; Okamura, H.; Tanaka, Y.; Mukae, H. Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy. Int. J. Biol. Sci. 2018, 14 (3), 331-340. DOI: 10.7150/ijbs.22809.

NLM
Senju H, Kumagai A, Nakamura Y, Yamaguchi H, Nakatomi K, Fukami S, Shiraishi K, Harada Y, Nakamura M, Okamura H, Tanaka Y, Mukae H. Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy. Int J Biol Sci 2018; 14(3):331-340. doi:10.7150/ijbs.22809. https://www.ijbs.com/v14p0331.htm

CSE
Senju H, Kumagai A, Nakamura Y, Yamaguchi H, Nakatomi K, Fukami S, Shiraishi K, Harada Y, Nakamura M, Okamura H, Tanaka Y, Mukae H. 2018. Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy. Int J Biol Sci. 14(3):331-340.

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