Harnessing the Power of Invariant Natural Killer T Cells in Cancer Immunotherapy

Invariant natural killer T (iNKT) cells are a distinct subset of innate-like lymphocytes bearing an invariant T-cell receptor, through which they recognize lipid antigens presented by monomorphic CD1d molecules. Upon activation, iNKT cells are capable of not only having a direct effector function but also transactivating NK cells, maturing dendritic cells, and activating B cells, through secretion of several cytokines and cognate TCR-CD1d interaction. Endowed with the ability to orchestrate an all-encompassing immune response, iNKT cells are critical in shaping immune responses against pathogens and cancer cells. In this review, we examine the critical role of iNKT cells in antitumor responses from two perspectives: (i) how iNKT cells potentiate antitumor immunity and (ii) how CD1d⁺ tumor cells may modulate their own expression of CD1d molecules. We further explore hypotheses to explain iNKT cell activation in the context of cancer and how the antitumor effects of iNKT cells can be exploited in different forms of cancer immunotherapy, including their role in the development of cancer vaccines.