α-galactosylceramide (KRN7000) suppression of chernical- and oncogene-dependent carcinogenesis

被引:114
作者
Hayakawa, Y
Rovero, S
Forni, G
Smyth, MJ [1 ]
机构
[1] Peter MacCallum Canc Ctr, Trescowthick Labs, Canc Immunol Program, Locked Bag 1,A Beckett St, Melbourne, Vic 8006, Australia
[2] Univ Turin, Dept Clin & Biol Sci, I-10043 Orbassano, Italy
[3] St Giovanni Battista Hosp, Ctr Expt Res & Med Studies, I-10126 Turin, Italy
关键词
D O I
10.1073/pnas.1630663100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Recent studies have revealed significant efficacy of the marine sponge glycolipid, a-galactosylceramide (alpha-GalCer), in treatment of experimental metastatic cancers, infections, and autoimmune diseases. However, the capacity of alpha-GalCer to prevent tumor development had never, to our knowledge, been evaluated in mouse models of chemical- and oncogene-dependent carcinogenesis. In this study, we demonstrate that long-term administration of soluble alpha-GalCer, spanning the time of tumor initiation, inhibits primary tumor formation in three different models: methylcholanthrene-induced sarcomas, mammary carcinomas in Her-2/neu transgenic mice, and spontaneous sarcomas in p53(-/-) mice. Weekly treatment of mice with alpha-GalCer maintained lymphoid tissue natural killer cell and T cell activation and elevated serum IFN-gamma and ILA concentrations. Consistent with the antimetastatic activity of alpha-GalCer, prevention of methylcholanthrene-induced sarcoma was IFN-gamma- and tumor necrosis factor-related apoptosis-inducing ligand dependent, but not perforin-dependent. Taken together, our results demonstrate that NK1.1(+)alphabetaTCR(+) cell-based immune therapy can inhibit primary tumorigenesis.
引用
收藏
页码:9464 / 9469
页数:6
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