title: Alpha-glycosylceramides enhance the antitumor cytotoxicity of hepatic lymphocytes obtained from cancer patients by activating CD3-CD56+ NK cells in vitro.
abstract: Alpha-glycosylceramides, such as alpha-galactosylceramide and alpha-glucosylceramide, induce antitumor immunity in various murine cancer models. In the murine hepatic metastasis model, V alpha 14 TCR+NK1.1+ T cells, which accumulate preferentially in the liver, are considered to play a key role in the induction of antitumor immunity by alpha-glycosylceramides. We recently reported that V alpha 24 TCR+ NKT cells, the human homologues of murine V alpha 14 TCR+NK1.1+ cells, are rarely seen among freshly isolated human hepatic lymphocytes. Therefore, it is important to examine whether alpha-glycosylceramides also enhance the antitumor cytotoxicity of human hepatic lymphocytes, as they have been shown to do in murine systems, to determine the usefulness of alpha-glycosylceramides in cancer immunotherapy in humans. Here, we show that alpha-glycosylceramides greatly enhance the cytotoxicity of human hepatic lymphocytes obtained from cancer patients against the tumor cell lines, K562 and Colo201, in vitro. The direct effector cells of the elicited cytotoxicity were CD3-CD56+ NK cells. Even though V alpha 24 TCR+NKT cells proliferated remarkably in response to alpha-glycosylceramides, they did not contribute directly to the cytotoxicity. Our observations strongly suggest the potential usefulness of alpha-glycosylceramides for immunotherapy of liver cancer in humans based on their ability to activate CD3-CD56+ NK cells in the liver.
authors.affiliation: Department of Research, Japanese Red Cross Central Blood Center, Tokyo, Japan. i-sochan@kt.rim.or.jp
authors.forename: S
authors.initials: S
authors.lastname: Ishihara
authors.forename: M
authors.initials: M
authors.lastname: Nieda
authors.forename: J
authors.initials: J
authors.lastname: Kitayama
authors.forename: T
authors.initials: T
authors.lastname: Osada
authors.forename: T
authors.initials: T
authors.lastname: Yabe
authors.forename: A
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Koezuka
authors.forename: S A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: H
authors.initials: H
authors.lastname: Nagawa
authors.forename: T
authors.initials: T
authors.lastname: Juji
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018949:Antigens, CD1 / Q000276:immunology; D055610:Antigens, CD1d; D000970:Antineoplastic Agents / Q000276:immunology*; D017252:CD3 Complex / Q000096:biosynthesis; D019002:CD56 Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D002518:Ceramides / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C119061:AGL 533; D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000970:Antineoplastic Agents; C526877:CD1D protein, human; D017252:CD3 Complex; D019002:CD56 Antigen; D002518:Ceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta