Fig. 4: Regulatory mechanisms of NKT cells.
NKT cells can be divided into two subtypes according to the different TCR expressed. Type I NKT cells secrete IFN-γ and TNF, recruit NK cells and CTL cells to mediate anti-tumor function. The use of α-GalCer can activate type I NKT cells to reduce the degree of LM in CRC patients. IL-12 can promote the secretion of IFN-γ by NKT, and IFN-γ can upregulate the IL-12 receptor of NKT in an autocrine manner, leading to the enhancement of the killing ability of NKT cells. Type II NKT does not normally recognize α-GalCer and plays a key role in tumor immune suppression. It can promote the generation of immunosuppressive cells such as Treg and MDSC. It can also secrete IL-13 and promote the immune escape of TCs through IL-4Rα-STAT6 signaling pathway. Increased production of IL-10 by NKT cells via MDSCs and induction of IL-10r expression by NK cells resulted in decreased NK cytotoxicity. Gut microbiota has the ability to regulate bile acid metabolism, which can increase IFN-γ production and promote the accumulation of liver NKT cells through the CXCL16-CXCR6 axis signaling pathway. NaB can increase NKT cells and Th17 cells and decrease Tregs, thereby increasing IL-17 and decreasing IL-10 secretion, thereby reducing the degree of LM. LPS preconditioning effectively enhanced the anti-tumor cytotoxicity of liver NK cells and NKT cells, reduced the expression of IFN-γ, and significantly reduced LM of colon cancer.
