1. Adoptive cell therapy (ACT): ACT involves isolating and expanding NK cells from a patient's own blood (autologous) or from a donor (allogenic), followed by their infusion back into the patient. The initial use of NK cells in treating cancer involved infusing IL-2-activated cells into patients in the 1980s. However, efficacy was limited due to IL-2 toxicity and unknown factors such as the impact of Treg cells. Later, evidence in 2002 indicated the clinical benefit of NK cells in patients receiving bone marrow transplants, showing lower relapse rates in certain conditions. Various trials involving adoptive cell transfer of activated NK cells demonstrated some success, especially when there was evidence of the cells persisting and expanding post-infusion. Recent studies have shown promise in enhancing NK cell efficiency by pre-activating them with a combination of cytokines, resulting in improved functions both in vitro and in vivo in mouse models of cancer. 140,141 2. Engineered NK cells: Recent research has shown achievements through the use of engineered NK cells containing activating chimeric antigen receptors (CARs) designed for targeting tumor-specific antigens. When CAR-NK cells developed from umbilical cord blood transduced with a modified retroviral vector expressing genes for an inducible caspase-9 suicide switch, an anti-CD19 CAR, and IL-15 were used to treat patients with CD19+ conditions, they exhibited favorable expansion, long-lasting presence, and positive outcomes, with no significant adverse effects observed 143 . 3. Combination therapies: NK cell-based therapies are often used in combination with other immunotherapies, such as immune checkpoint inhibitors or monoclonal antibodies, to enhance their efficacy 144 by overcoming tumor immunosuppression and promoting more robust antitumor immune responses. Typical immune checkpoint PD-1/CTLA-4 inhibitors have been used not only in relieving the inhibitory state of T cells but also to reverse the incapacity of NK cell. 145 4. Targeting inhibitory receptors: Strategies are being explored to block or downregulate inhibitory receptors on NK cells, such as NKG2A, to overcome tumorinduced immunosuppression and enhance NK cell activity. Despite their great promise challenges remain in NK cell-based immunotherapy, including optimizing NK cell expansion and persistence, improving homing to tumor sites, and overcoming immunosuppressive tumor microenvironments. Ongoing research and clinical trials are aimed at addressing these challenges and further unlocking the therapeutic potential of NK cells in cancer treatment. A few of these clinical trials are listed in Table to show a snapshot of this currently active clinical trial landscape. Tumor-associated macrophages (TAMs): Reprogramming the tumor microenvironment Tumor-associated macrophages (TAMs), a type of immune cell that infiltrates the tumor microenvironment and plays a crucial role in tumor progression and immunosuppression, are derived from circulating monocytes that recruited to the tumor site by various chemokines and cytokines produced by the tumor cells. Generally, TAMs can be classified into two main phenotypes: M1 and M2. The M1 phenotype, also known as classically activated macrophages, is associated with pro-inflammatory responses and antitumor activity. In contrast, the phenotype, also called alternatively activated macrophages, exhibits anti-inflammatory properties, and promotes tumor growth, angiogenesis, tissue remodeling, and immunosuppression. Listed below are ways in which TAMs are currently being explored in cancer immunotherapy: