NK cells are innate lymphoid cells with potent cytolytic function that play a critical role in immune surveillance against cancer. Recent research highlights their importance in cancer immunotherapy and explores new strategies to target NK cells for cancer treatment. NK cells recognize and kill infected or tumor cells through a balance of activating and inhibitory signals delivered by surface receptors. They can detect 'missing self' by the loss of MHC class I molecules or by upregulating ligands that override inhibitory signals. NK cells are 'ready to kill' and can rapidly respond to tumor cells, making them valuable for immunotherapy. NK cells express various receptors, including NKG2D, NKp46, NKp30, and DNAM1, which recognize ligands on tumor cells. These receptors are crucial for NK cell activation and tumor recognition. Tumor cells can evade NK cell surveillance by shedding NKG2D ligands, downregulating NKG2D, or expressing inhibitory ligands. Therapeutic strategies aim to enhance NK cell activity by blocking inhibitory receptors, such as KIRs and NKG2A, or by using agonist antibodies to activate NK cell receptors. NK cells can be genetically modified to express chimeric antigen receptors (CARs) that target tumor-specific antigens, enhancing their antitumor activity. CAR-expressing NK cells show promise in clinical trials, with improved efficacy compared to traditional therapies. Additionally, bispecific antibodies that redirect NK cells to tumor cells are being developed to enhance NK cell-mediated cytotoxicity. Despite their potential, challenges remain in optimizing NK cell-based therapies, including overcoming inhibitory signals, enhancing NK cell trafficking to tumors, and reducing systemic toxicity. Future research aims to combine NK cell-based therapies with other immunotherapies, such as checkpoint inhibitors, to improve cancer treatment outcomes. NK cells are promising candidates for CAR-based therapies due to their diverse activating receptors and ability to spontaneously lyse tumors. Overall, NK cells represent a significant area of research in cancer immunotherapy, with potential to enhance antitumor immune responses through various therapeutic approaches.NK cells are innate lymphoid cells with potent cytolytic function that play a critical role in immune surveillance against cancer. Recent research highlights their importance in cancer immunotherapy and explores new strategies to target NK cells for cancer treatment. NK cells recognize and kill infected or tumor cells through a balance of activating and inhibitory signals delivered by surface receptors. They can detect 'missing self' by the loss of MHC class I molecules or by upregulating ligands that override inhibitory signals. NK cells are 'ready to kill' and can rapidly respond to tumor cells, making them valuable for immunotherapy. NK cells express various receptors, including NKG2D, NKp46, NKp30, and DNAM1, which recognize ligands on tumor cells. These receptors are crucial for NK cell activation and tumor recognition. Tumor cells can evade NK cell surveillance by shedding NKG2D ligands, downregulating NKG2D, or expressing inhibitory ligands. Therapeutic strategies aim to enhance NK cell activity by blocking inhibitory receptors, such as KIRs and NKG2A, or by using agonist antibodies to activate NK cell receptors. NK cells can be genetically modified to express chimeric antigen receptors (CARs) that target tumor-specific antigens, enhancing their antitumor activity. CAR-expressing NK cells show promise in clinical trials, with improved efficacy compared to traditional therapies. Additionally, bispecific antibodies that redirect NK cells to tumor cells are being developed to enhance NK cell-mediated cytotoxicity. Despite their potential, challenges remain in optimizing NK cell-based therapies, including overcoming inhibitory signals, enhancing NK cell trafficking to tumors, and reducing systemic toxicity. Future research aims to combine NK cell-based therapies with other immunotherapies, such as checkpoint inhibitors, to improve cancer treatment outcomes. NK cells are promising candidates for CAR-based therapies due to their diverse activating receptors and ability to spontaneously lyse tumors. Overall, NK cells represent a significant area of research in cancer immunotherapy, with potential to enhance antitumor immune responses through various therapeutic approaches.