Natural Killer (NK) cells in immunotherapy and perspectives in antitumour approaches

Natural Killer (NK) cells comprise a group of specialized innate lymphoid cells endowed with multiple cytotoxicity mechanisms while also harnessed with the ability to enhance other immune cells with cytokine production. This exclusive advantage of them to recognize and eliminate virally infected cells and tumour cells has been unmasked for decades, and previous clinical trials are also successfully tested for both efficacy and safety. With the emerging strategies in CAR-T cell therapy, such technologies can also be capable of further enhancing the viability of NK cell immunotherapy through cytokine armouring, chimeric antigen receptor (CAR) transduction, checkpoint inhibition, and co-stimulatory signals. Other than the conventional approach of engineering CAR to target tumour antigens, they are also capable of acting as blockers to the inhibitory compartments on tumour cells within the harsh environment to reduce the negative effects. Despite all these aspects, the tumour microenvironment (TME) is another essential facet when discussing cancer therapy owing to its characteristic setting that contributes immensely to immune evasion and immune function inhibition. In this review, I introduce the foundational mechanism for NK cytotoxicity and its signalling routes, discuss the impacts of TME on immune cells and their antitumour effects, evaluate possible strategies that overcome the current challenges, and propose a few potentially adoptive measures for future research in general immunotherapy from a perspective of molecular biology