Metastasis is the major cause of cancer-related deaths. Invasive primary cancers often metastasize after circulating tumor cells (CTCs) enter the bloodstream or lymph node to colonize adjacent tissue or distant anatomical locations. CTCs interact with immune cells and metastatic microenvironments, survival signaling, and chemotherapeutic resistance. Among immune cells, natural killer (NK) cells can, directly and indirectly, interact with CTCs to control cancer metastasis. Understanding the molecular mechanisms that drive NK cells mediated recognition and elimination of CTCs may pave the way for a new generation of anti-CTC molecularly targeted immunotherapies. In this review, we will discuss i) the role of CTCs in metastases, ii) CTCs in the context of the tumor microenvironment, iii) CTCs immune escape, and finally, iv) the potentials of NK cell-based therapies alone, or in combination with nanomedicine for targeted-immunotherapies of metastatic diseases.

转移是癌症相关死亡的主要原因。侵袭性原发癌通常在循环肿瘤细胞（CTC）进入血流或淋巴结进入附近组织或遥远的解剖位置后转移。CTC与免疫细胞和转移性微环境，生存信号和化疗耐药性相互作用。在免疫细胞中，自然杀伤（NK）细胞可以直接和间接与CTC相互作用以控制癌症转移。了解驱动NK细胞介导的CTC识别和消除的分子机制可能为新一代抗CTC铺平道路-CTC分子靶向免疫疗法。在这篇综述中，我们将讨论i）CTC在转移中的作用，ii）CTC在肿瘤微环境的背景下，iii）CTC的免疫逃逸，最后，iv）单独基于NK细胞疗法的潜力，或与纳米药物联合用于转移性疾病的靶向免疫治疗。