Simple Summary Cell-based oncotherapies are gaining considerable terrain in the last years thanks to the development of safe and promising treatments against cancer. A better understanding of the roles and functional capacities of cellular immune components displaying antitumor activity will likely potentiate these encouraging results. In this review, we summarize the properties and uses of a particular type of immune cells that recognize lipid-derived determinants presented on the cell surface. Such immune cells, known as invariant Natural Killer T (iNKT) cells have the potential to significantly favor anti-tumoral adaptive immune responses. Currently, they are being extensively evaluated in preclinical settings and may soon reach clinical trials to ameliorate anti-cancer treatments. Abstract Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.
【저자키워드】 Inflammation, Immunotherapy, Cancer, Infectious disease, Antigen presentation, natural killer T cells (NKTs),