PD-1-positive Natural Killer Cells have a weaker antitumor function than that of PD-1-negative Natural Killer Cells in Lung Cancer

Niu, Chao; Li, Min; Zhu, Shan; Chen, Yongchong; Zhou, Lei; Xu, Dongsheng; Xu, Jianting; Li, Zhaozhi; Li, Wei; Cui, Jiuwei

doi:10.7150/ijms.47701

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Theranostics

International Journal of Biological Sciences

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Int J Med Sci 2020; 17(13):1964-1973. doi:10.7150/ijms.47701 This issue Cite

Research Paper

PD-1-positive Natural Killer Cells have a weaker antitumor function than that of PD-1-negative Natural Killer Cells in Lung Cancer

Chao Niu^1*, Min Li^1*, Shan Zhu^2*, Yongchong Chen¹, Lei Zhou¹, Dongsheng Xu¹, Jianting Xu¹, Zhaozhi Li¹, Wei Li¹, Jiuwei Cui^1✉

1. Department of Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
2. Department of Translational Medicine, The First Hospital of Jilin University, Changchun 130021, China.
*Equal contributors.

Citation:

Niu C, Li M, Zhu S, Chen Y, Zhou L, Xu D, Xu J, Li Z, Li W, Cui J. PD-1-positive Natural Killer Cells have a weaker antitumor function than that of PD-1-negative Natural Killer Cells in Lung Cancer. Int J Med Sci 2020; 17(13):1964-1973. doi:10.7150/ijms.47701. https://www.medsci.org/v17p1964.htm

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Abstract

Antibodies targeting the immune checkpoint inhibitor, programmed cell death 1 (PD-1), have provided a breakthrough in the treatment of lung cancer. However, the function of PD-1 in natural killer (NK) cells of cancer patients remains unclear. Herein, we analyzed the expression of PD-1 on the NK cells in the peripheral blood of patients with lung cancer and found that the level of PD-1⁺ NK cells in patients was significantly higher than that in healthy individuals. Moreover, these PD-1⁺ NK cells demonstrated a weaker ability to secrete interferon-gamma (INF-γ), granzyme B, and perforin, and exhibited lower CD107a expression. Importantly, in patients with lung cancer, the percentage of PD-1⁺ NK cells was significantly positively correlated with the concentration of IL-2 in the plasma, which was also higher than that in healthy individuals. In addition, IL-2 could increase the expression of PD-1 on NK cells in vitro, indicating that high IL-2 level in the plasma is largely responsible for the abundance of PD-1⁺ NK cells in patients with lung cancer. These findings demonstrate intriguing mechanisms for understanding the expression of PD-1 on NK cells and the function of PD-1⁺ NK cells in lung cancer. This study confirms and extends previous studies demonstrating that PD-1 can negatively regulate the antitumor function of NK cells.

Keywords: natural killer cells, programmed death-1, cytotoxicity, lung cancer

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APA

Niu, C., Li, M., Zhu, S., Chen, Y., Zhou, L., Xu, D., Xu, J., Li, Z., Li, W., Cui, J. (2020). PD-1-positive Natural Killer Cells have a weaker antitumor function than that of PD-1-negative Natural Killer Cells in Lung Cancer. International Journal of Medical Sciences, 17(13), 1964-1973. https://doi.org/10.7150/ijms.47701.

ACS

Niu, C.; Li, M.; Zhu, S.; Chen, Y.; Zhou, L.; Xu, D.; Xu, J.; Li, Z.; Li, W.; Cui, J. PD-1-positive Natural Killer Cells have a weaker antitumor function than that of PD-1-negative Natural Killer Cells in Lung Cancer. Int. J. Med. Sci. 2020, 17 (13), 1964-1973. DOI: 10.7150/ijms.47701.

NLM

CSE

Niu C, Li M, Zhu S, Chen Y, Zhou L, Xu D, Xu J, Li Z, Li W, Cui J. 2020. PD-1-positive Natural Killer Cells have a weaker antitumor function than that of PD-1-negative Natural Killer Cells in Lung Cancer. Int J Med Sci. 17(13):1964-1973.

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