Natural killer T cell-mediated antitumor immune responses and their clinical applications.
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.
Seino
Ken-ichiro
K
Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
Motohashi
Shinichiro
S
Fujisawa
Takehiko
T
Nakayama
Toshinori
T
Taniguchi
Masaru
M
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d; D002450:Cell Communication / Q000276:immunology; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; C493154:alpha-galactosylceramide