Abstract
Natural killer T cells are T lymphocytes with unique activation and effector properties. The majority of NKT cells, termed type-I or iNKT cells, recognize lipid antigens presented on MHC-like CD1d molecules. Type-I NKT cells have the capacity to rapidly secrete various cytokines upon activation, thereby regulate immune responses exerts dominant anti-tumor and anti-microbial effector functions. Specific activation of type-I NKT cells in mouse models boosts immunity and prevents metastasis, which has led to a number of phase I-II clinical trials. Since the discovery of NKT cells other subsets with different specificities and effector functions have been described. This article briefly reviews the physiological functions of NKT cell subsets, their implications in cancer and the attempts that have been made to employ NKT cells for immune therapy of cancer.
Highlights
Natural killer T cells are T lymphocytes with unique activation and effector properties
Natural killer T (NKT) cells are a subset of innate lymphocytes with unique activation and effector properties
Type-I NKT cells activated by CD1d: D-GC complexes secrete IL-4 within minutes after activation, which is followed by a sustained secretion of IFNJ, displaying opposite biological functions to IL-4
Summary
Natural killer T (NKT) cells are a subset of innate lymphocytes with unique activation and effector properties. Upon TCR-mediated activation type-I NKT cells produce various cytokines, of which some may have opposite functions. Type-I NKT cells activated by CD1d: D-GC complexes secrete IL-4 within minutes after activation, which is followed by a sustained secretion of IFNJ, displaying opposite biological functions to IL-4. This bi-functional cytokine secretion profile has led to the development of several D-GC modifications stimulating a pronounced Th1 cytokine profile and increased anti-tumor activity observed in murine cancer models [28,29,30,31]. Prostate tumor cells by expressing CD1d molecules inhibit the activation of IFNJ secretion by type-I NKT cells [38]. NKT-mediated killing of early stage myeloma cells which express CD1d molecules is lost upon transition to advanced myeloma stage and subsequent loss of CD1d expression [40]
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