ß-mannosylceramide activates type I natural killer t cells to induce tumor immunity without inducing long-term functional anergy.
Clin Cancer Res
; 19(16): 4404-11, 2013 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-23804426
ABSTRACT
PURPOSE:
Most studies characterizing antitumor properties of invariant natural killer T (iNKT) cells have used the agonist, α-galactosylceramide (α-GalCer). However, α-GalCer induces strong, long-lasting anergy of iNKT cells, which could be a major detriment for clinical therapy. A novel iNKT cell agonist, ß-mannosylceramide (ß-ManCer), induces strong antitumor immunity through a mechanism distinct from that of α-GalCer. The objective of this study was to determine whether ß-ManCer induces anergy of iNKT cells. EXPERIMENTALDESIGN:
Induction of anergy was determined by ex vivo analysis of splenocytes from mice pretreated with iNKT cell agonists as well as in the CT26 lung metastasis in vivo tumor model.RESULTS:
ß-ManCer activated iNKT cells without inducing long-term anergy. The transience of anergy induction correlated with a shortened duration of PD-1 upregulation on iNKT cells activated with ß-ManCer, compared with α-GalCer. Moreover, whereas mice pretreated with α-GalCer were unable to respond to a second glycolipid stimulation to induce tumor protection for up to 2 months, mice pretreated with ß-ManCer were protected from tumors by a second stimulation equivalently to vehicle-treated mice.CONCLUSIONS:
The lack of long-term functional anergy induced by ß-ManCer, which allows for a second dose to still give therapeutic benefit, suggests the strong potential for this iNKT cell agonist to succeed in settings where α-GalCer has failed.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ceramides
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Clonal Anergy
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Natural Killer T-Cells
/
Neoplasms
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2013
Document type:
Article
Affiliation country: