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Cancer Sci. 2006 Sep;97(9):807-12. Epub 2006 Jun 29.

Natural killer T cell-mediated antitumor immune responses and their clinical applications.

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Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.


A unique lymphocyte population, CD1d-restricted NKT cells, has been revealed to be a key player in both the innate and acquired immune responses, including antitumor effects. Recent studies revealed that at least two subsets of CD1d-restricted NKT cells exist: type I, having invariant Valpha14 receptor; and type II, having heterogeneous non-Valpha14 receptor. The specific glycolipid ligand, alpha-GalCer, effectively stimulates mouse and human type I NKT cells. The activation of type I NKT cells substantially influences function of other various cell types, particularly DC, NK cells, CD4 Th1 cells, and CD8 cytotoxic T cells, all contributing to the antitumor immune responses. Recent studies also indicated that, unlike type I NKT cells, type II NKT cells have a potential to repress antitumor immune responses. In this review, we summarize the characteristics of the antitumor immune responses mediated by both mouse and human CD1d-restricted NKT cells and discuss their potential in clinical applications against cancer.

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