NK cells-directed therapies target circulating tumor cells and metastasis.

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.