Figure 2.
Activated NKT cells can mount both direct and indirect anti-tumor responses. Following activation, NKT cells rapidly secrete cytokines, such as IFN-γ, which can promote the activation of NK cells and CD8+ T cells, and in combination with CD40/CD40L interactions can also lead to the maturation of dendritic cells which can secrete IL-12 and further enhance NK and CD8+ T cell activation. NKT cells can also directly mediate cytotoxicity through FAS/FASL, perforin, and granzyme. NKT cells may be directed towards tumor cells expressing specific antigen through the transduction and expression of chimeric antigen receptors (CAR). CARs have an extracellular antigen-targeting domain capable of binding their target antigen in an MHC-independent manner. Current research efforts are focused on harnessing the adaptability of CARs to enhance NKT cell targeting of tumors.