Immune checkpoints HLA-E:CD94-NKG2A and HLA-C:KIR2DL1 complementarily shield circulating tumor cells from NK-mediated immune surveillance

作者：Xiaowei Liu, Fengli Zuo, Jinen Song, Leyi Tang, Xueyan Wang, Xinyu Liu, Hao Zhang, Zhankun Yang, Jing Jing, Xuelei Ma, Hubing Shi · 发表于：Cell Discovery · 年份：2024 · DOI：10.1038/s41421-024-00646-3 · 被引用次数：27 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、CAR-T cell therapy research

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.