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, Min Li, Shan Zhu, Yongchong Chen, Lei Zhou, Dongsheng Xu, Jianting Xu, Zhaozhi Li, Wei Li, Jiuwei Cui
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-), 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.