Engineered NK Cells: A Breakthrough Strategy to Overcome CancerImmunosuppression

Cancer's ability to manipulate the immune system through tumor-induced immunosuppressionremains a significant challenge in oncology. The tumor microenvironment (TME)employs various mechanisms, including the recruitment of immunosuppressive cells, the secretionof inhibitory cytokines, and metabolic reprogramming, to evade immune responses andimpair immunotherapies. Natural killer (NK) cells, a vital component of innate immunity, exhibitpotent anti-tumor activity. However, their function is often suppressed within the TME.Recent advancements in genetic engineering have enabled the development of modified NKcells with enhanced persistence, targeting, and cytotoxicity. Strategies such as chimeric antigenreceptor (CAR)-NK cells, cytokine engineering, immune checkpoint blockade, and resistance toTME factors have demonstrated promising potential in overcoming immunosuppression andimproving cancer therapy. This review explores the role of engineered NK cells in counteractingtumor-mediated immune evasion, current clinical advancements, and future directions inNK cell-based immunotherapy. While challenges such as in vivo persistence, scalability, andoff-target effects remain, engineered NK cells offer a promising avenue for enhancing cancertreatment efficacy. This review aims to synthesize advancements in engineered NK cell therapiesto overcome tumor-mediated immunosuppression.