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

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 Niu1*, Min Li1*, Shan Zhu2*, Yongchong Chen1, Lei Zhou1, Dongsheng Xu1, Jianting Xu1, Zhaozhi Li1, Wei Li1, Jiuwei Cui1✉

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.

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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. Available from http://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