Natural killer (NK) cells are innate immune cells critically involved in the control of cancer. Their important role in cancer immunity reflects the ability of NK cells to recognize malignant cells through an array of germline-encoded receptors expressed on their surface, enabling NK cells to detect and rapidly kill tumor cells through targeted cytotoxicity. In addition to their cytotoxic activity, NK cells fulfill a fundamental and often underappreciated role in the local orchestration of cancer immunity through their ability to communicate with innate and adaptive immune cells within the tumor microenvironment (TME), which is achieved through the secretion of multiple chemokines, cytokines, and growth factors. Within tumor tissue, NK cells regulate the recruitment, survival and functional activity of various immune cells including monocytes, granulocytes, dendritic cells and T cells, thereby shaping intratumoral immune cell composition and functionality. Emerging evidence further suggest a role of NK cells in the regulation of stromal cells within the TME. Here, we discuss key aspects of NK cell communication with other intratumoral cell types and its role for cancer immunity. Strategies aimed at boosting anti-cancer immunity by enhancing NK cell communication and functionality within tumor tissue provide attractive new ways for treatment of cancer patients.
Keywords: Cancer immunity; Immune cell cross-talk; Immune evasion; Immunotherapy; NK cells; Tumor microenvironment.
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