Cancer’s ability to manipulate the immune system through tumor-induced immunosuppression remains a significant challenge in oncology. The tumor microenvironment (TME) employs various mechanisms, including the recruitment of immunosuppressive cells, the secretion of inhibitory cytokines, and metabolic reprogramming, to evade immune responses and impair immunotherapies. Natural killer (NK) cells, a vital component of innate immunity, exhibit potent anti-tumor activity. However, their function is often suppressed within the TME. Recent advancements in genetic engineering have enabled the development of modified NK cells with enhanced persistence, targeting, and cytotoxicity. Strategies such as chimeric antigen receptor (CAR)-NK cells, cytokine engineering, immune checkpoint blockade, and resistance to TME factors have demonstrated promising potential in overcoming immunosuppression and improving cancer therapy. This review explores the role of engineered NK cells in counteracting tumor-mediated immune evasion, current clinical advancements, and future directions in NK cell-based immunotherapy. While challenges such as in vivo persistence, scalability, and off-target effects remain, engineered NK cells offer a promising avenue for enhancing cancer treatment efficacy. This review aims to synthesize advancements in engineered NK cell therapies to overcome tumor-mediated immunosuppression.
Kumar et al. (Thu,) studied this question.
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