Immune checkpoints HLA-E:CD94-NKG2A and HLA-C:KIR2DL1 complementarily shield circulating tumor cells from NK-mediated immune surveillance
Xiaowei Liu, Fengli Zuo, Jinen Song, Leyi Tang, Xueyan Wang, Xinyu Liu, Hao Zhang, Zhankun Yang, Jing Jing, Xuelei Ma, Hubing Shi
Abstract
Tumor metastasis is the leading cause of cancer-related deaths 1 . Circulating tumor cells (CTCs), shed from the primary tumor, play a “seed” role in initiating the formation of metastatic lesions 2 . Identifying immune checkpoints on CTCs may provide novel immunotherapy strategies to prevent tumor metastasis. Recently, we have unraveled that natural killer cells (NKs) play a predominant role in immune surveillance on CTCs, and CTCs escape the surveillance by engaging an immune checkpoint HLA-E:CD94-NKG2A 3 . Blockade of this immune checkpoint significantly prevents tumor metastasis by eliminating CTCs. Our results provide a potential strategy to prevent CTC-mediated tumor metastasis by disrupting the immune checkpoint between CTCs and NKs. However, due to the diversity of NKs 4 , 5 , many researchers raise a question of whether or not other immune checkpoints also facilitate the escape of immune surveillance in addition to the reported molecular pair 6 . Identifying the immune checkpoint molecules between CTCs and other subtypes of NKs may provide a comprehensive strategy for prevention of tumor metastasis by activating NK-mediated CTCs elimination.