NKT cells-a generalist in disease treatment and a new key to unlock immunotherapy.

NKT cells (natural killer T cells) are a subpopulation of specialized T cells that recognize lipid antigens presented by CD1d molecules, which can be classified into type I NKT cells, type II NKT cells and NKT-like cells. NKT cells play a key role in linking innate and adaptive immunity. In recent years, NKT cells have been found to be involved in the development of various systemic diseases, including tumors, respiratory system diseases, autoimmune diseases, reproductive system diseases, gastrointestinal system diseases and liver diseases. Thus, immunotherapy targeting NKT cells has brought novel strategies for the treatment of cancers and other diseases. Currently, NKT cell-based immunotherapy includes NKT cell agonist, CAR-NKT and NKT gene editing. Among them, α-galactosylceramide (α-GalCer), a NKT cell agonist, has demonstrated promising applications in enhancing vaccine immunogenicity and anti-tumor immunity. In conclusion, this review systematically summarizes the development, differentiation, classification, and function of NKT cells, as well as their relationships with systemic diseases. Additionally, this review also emphasizes the prospects for the clinical application of NKT cell-based immunotherapy. Future research should focus on the development of novel NKT cell-targeted therapeutic strategies and vaccine adjuvants to advance personalized medicine and precision immunotherapy.