Immunomodulation of NK Cells by Ionizing Radiation
Jiarui Chen, Xingyu Liu, Zihang Zeng, Jiali Li, Yuan Luo, Wenjie Sun, Yan Gong, Junhong Zhang, Qiuji Wu, Conghua Xie
Abstract
Natural killer (NK) cells play a critical role in the antitumor immunity. Ionizing radiation (IR) has a pronounced effect on modifying NK cell biology, while the molecular mechanisms remain elusive. In this review, we briefly introduce the anti-tumor activity of NK cells and summarize the impact of IR on NK cells both directly and indirectly. On one hand, low-dose ionizing radiation (LDIR) activates NK functions while high-dose ionizing radiation (HDIR) is likely to partially impair NK functions, which can be reversed by interleukin (IL)-2 pretreatment. On the other hand, NK functions may be adjusted by other immune cells and the alternated malignant cell immunogenicity under the settings of IR. Various immune cells, such as the tumor-associated macrophage (TAM), dendritic cell (DC), regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC), and tumor exhibited ligands, such as the natural killer group 2 member D ligand (NKG2DL), natural cytotoxicity receptors (NCR) ligand, TNF-related apoptosis-inducing ligand-receptor (TRAIL-R), and FAS, have been involved in this process. Better understanding the molecular basis is a promising way in which to augment NK-cell-based antitumor immunity in combination with IR.