PMID- 17312129
OWN - NLM
STAT- MEDLINE
DCOM- 20070424
LR  - 20220228
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 5
DP  - 2007 Mar 1
TI  - Tumor cells loaded with alpha-galactosylceramide induce innate NKT and NK 
      cell-dependent resistance to tumor implantation in mice.
PG  - 2853-61
AB  - Dendritic cells (DCs) loaded with alpha-galactosylceramide (alpha-GalCer) are 
      known to be active APCs for the stimulation of innate NKT and NK cell responses 
      in vivo. In this study, we evaluated the capacity of non-DCs to present 
      alpha-GalCer in vitro and in vivo, particularly tumor cells loaded with 
      alpha-GalCer (tumor/Gal). Even though the tumor cells lacked expression of CD40, 
      CD80, and CD86 costimulatory molecules, the i.v. injection of tumor/Gal resulted 
      in IFN-gamma secretion by NKT and NK cells. These innate responses to tumor/Gal, 
      including the induction of IL-12p70, were comparable to or better than 
      alpha-GalCer-loaded DCs. B16 melanoma cells that were stably transduced to 
      express higher levels of CD1d showed an increased capacity relative to wild-type 
      B16 cells to present alpha-GalCer in vivo. Three different tumor cell lines, when 
      loaded with alpha-GalCer, failed to establish tumors upon i.v. injection, and the 
      mice survived for at least 6 mo. The resistance against tumor cells was 
      independent of CD4 and CD8 T cells but dependent upon NKT and NK cells. Mice were 
      protected from the development of metastases if the administration of live B16 
      tumor cells was followed 3 h or 3 days later by the injection of 
      CD1d(high)-alpha-GalCer-loaded B16 tumor cells with or without irradiation. Taken 
      together, these results indicate that tumor/Gal are effective APCs for innate NKT 
      and NK cell responses, and that these innate immune responses are able to resist 
      the establishment of metastases in vivo.
FAU - Shimizu, Kanako
AU  - Shimizu K
AD  - Research Unit for Cellular Immunotherapy, RIKEN Research Center for Allergy and 
      Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
FAU - Goto, Akira
AU  - Goto A
FAU - Fukui, Mikiko
AU  - Fukui M
FAU - Taniguchi, Masaru
AU  - Taniguchi M
FAU - Fujii, Shin-ichiro
AU  - Fujii S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (Galactosylceramides)
RN  - 0 (alpha-galactosylceramide)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antigens, CD/immunology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Galactosylceramides/*immunology
MH  - Graft Rejection/immunology
MH  - *Immunity, Innate
MH  - Interferon-gamma/immunology
MH  - Interleukin-12/immunology
MH  - Killer Cells, Natural/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Neoplasm Transplantation/immunology
MH  - Neoplasms, Experimental/*immunology
MH  - T-Lymphocytes/*immunology
EDAT- 2007/02/22 09:00
MHDA- 2007/04/25 09:00
CRDT- 2007/02/22 09:00
PHST- 2007/02/22 09:00 [pubmed]
PHST- 2007/04/25 09:00 [medline]
PHST- 2007/02/22 09:00 [entrez]
AID - 178/5/2853 [pii]
AID - 10.4049/jimmunol.178.5.2853 [doi]
PST - ppublish
SO  - J Immunol. 2007 Mar 1;178(5):2853-61. doi: 10.4049/jimmunol.178.5.2853.