Harnessing the power of memory-like NK cells to fight cancer

Abstract

Summary Natural killer (NK) cells possess the innate ability to eliminate cancerous cells effectively. Their crucial role in immunosurveillance has been widely recognized and exploited for therapeutic intervention. Despite the fast-acting nature of NK cells, NK adoptive cell transfer lacks favorable response in some patients. Patient NK cells often display diminished phenotype in preventing cancer progression resulting in poor prognosis. Tumor microenvironment plays a significant role in causing the downfall of NK cells in patients. The release of inhibitory factors by tumor microenvironment hinders normal function of NK cells against tumor. To overcome this challenge, therapeutic strategies such as cytokine stimulation and genetic manipulation are being investigated to improve NK tumor-killing capacity. One of the promising approaches includes generation of more competent NK cells via ex vivo cytokines activation and proliferation. Cytokine-induced ML-NK demonstrated phenotypic alterations such as enhanced expression of activating receptors which help elevate their antitumor response. Previous preclinical studies showed enhanced cytotoxicity and IFNγ production in ML-NK cells compared to normal NK cells against malignant cells. Similar effects are shown in clinical studies in which MK–NK demonstrated encouraging results in treating hematological cancer. However, there is still a lack of in-depth studies using ML-NK in treating different types of tumors and cancers. With convincing preliminary response, this cell-based approach could be used to complement other therapeutic modalities to achieve better clinical outcomes.