Abstract
Natural killer T (NKT) cells are specialized CD1d-restricted T cells that recognize lipid antigens. Following stimulation, NKT cells lead to downstream activation of both innate and adaptive immune cells in the tumor microenvironment. This has impelled the development of NKT cell-targeted immunotherapies for treating cancer. In this review, we provide a brief overview of the stimulatory and regulatory functions of NKT cells in tumor immunity as well as highlight preclinical and clinical studies based on NKT cells. Finally, we discuss future perspectives to better harness the potential of NKT cells for cancer therapy.
Highlights
Both innate and adaptive immune systems respond to tumor cells and participate in immunesurveillance against tumor [1]
We have shown that lysophosphatidylcholine (LPC), lysophospholipid markedly upregulated in myeloma patients was an antigen for human type II natural killer T (NKT) cells [58]
NKT cells have been generated from CD34+ cells isolated from cord blood using IL-15 and stem cell factor in liquid culture system
Summary
Both innate and adaptive immune systems respond to tumor cells and participate in immunesurveillance against tumor [1]. De Santo et al reported type I NKT cell-mediated reversal of immunosuppressive activity of neutrophils in melanoma, serum amyloid A1 (SAA-1) derived as consequence of tumor-associated inflammation induced differentiation of IL-10-producing neutrophils causing suppression of antigen-specific T cell responses. Administration of soluble α-GalCer leads to activation and expansion of type I NKT cells, creating a milieu of immune-stimulatory cytokines including IFN-γ and costimulatory molecules, resulting in maturation of host APC enhancing antitumor T cell response. A big improvement of this approach is CD1d-mediated cross-presentation of endogenous glycolipids and or α-GalCer from tumor cells to NKT cells, leading to DC maturation and effective long-term T cell resistance to the tumor [128] Another approach involved adoptive transfer of ex vivo expanded and or activated type I NKT cells to restore type I NKT cell numbers in preclinical models of melanoma and lymphoid neoplasms [194, 196, 208]. Prevention of tumor at early stages NKT and NK activation α-GalCer (i.p.) 2 μg single dose
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