Enhanced Antitumor Effects by Chemical Modified IGb3 Analogues

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	Enhanced Antitumor Effects by Chemical Modified IGb3 Analogues
	Zhou, Zhixia 1; Zhang, Cai 1; Xia, Chengfeng 3; Chen, Wenlan 4,5; Zhu, Huawei 2; Shang, Pingping 1; Ma, Fang 1; Wang, Peng George 4,5; Zhang, Jian 1; Xu, Wenfang 2
刊名	MOLECULAR CANCER THERAPEUTICS
	2011-08-01
卷号	10 期号:8 页码:1375-1384
关键词	V-ALPHA-14I NKT CELLS KILLER T-CELLS IFN-GAMMA PRODUCTION ALPHA-GALACTOSYLCERAMIDE AUTOIMMUNE ENCEPHALOMYELITIS IMMUNE-RESPONSES DENDRITIC CELLS ACTIVATION BET GATA-3
ISSN号	1535-7163
通讯作者	Zhang, C (reprint author), Shandong Univ, Inst Immunopharmacol & Immunotherapy, Sch Pharmaceut Sci, 44 Wenhua,West Rd, Jinan 250012, Peoples R China
英文摘要	Certain glycolipid antigens for natural killer T (NKT) cells can direct the overall cytokine balance of the immune response. However, the molecular mechanism of Th1- or Th2-biased cytokine secretion by NKT cells is still unknown. Previously, we synthesized isoglobotrihexosylceramide (iGb3) analogues by introducing a hydroxyl group at C4 on the ceramide portion of iGb3 to produce 4-HO-iGb3 or to further deoxylation on the terminal galactose to produce 4'"-dh-iGb3. Both modified iGb3, especially 4'"-dh-iGb3, stimulated more IFN-gamma production by hepatic NKT cells, and thus elicited preferential Th1 responses. Here, we found that 4'"-dh-iGb3-loaded bone marrow-derived dendritic cells (DC) could significantly inhibit growth of subcutaneous melanoma and suppress lung metastasis in C57BL/6 mice compared with unmodified iGb3-loaded DCs. In investigating the mechanisms of this improved activity, we found that 4'"-dh-iGb3 stimulation increased STAT1 signaling by NKT cells, whereas the phosphorylation of Th2 type cytokine-associated transcription factor STAT6 signaling was not affected. Analysis of the structures of iGb3 and 4'"-dh-iGb3 revealed that 4'"-dh-iGb3 provides greater stability and affinity between glycolipid and CD1d or NKT TCR complex than iGb3. Thus, 4'"-dh-iGb3 can improve the antitumor effects of a DC-based vaccine possibly by stabilizing the CD1d/glycolipid/TCR complex and stimulating IFN-gamma signaling of NKT cells. Furthermore, chemical modification of iGb3 can elicit Th1-biased responses by NKT cells, and 4'"-dh-iGb3 combined with a DC vaccine may serve as a potent new NKT-based therapy against tumors and infectious diseases. Mol Cancer Ther; 10(8); 1375-84. (C) 2011 AACR.
学科主题	Oncology
类目[WOS]	Oncology
研究领域[WOS]	Oncology
关键词[WOS]	V-ALPHA-14I NKT CELLS ; KILLER T-CELLS ; IFN-GAMMA PRODUCTION ; ALPHA-GALACTOSYLCERAMIDE ; AUTOIMMUNE ENCEPHALOMYELITIS ; IMMUNE-RESPONSES ; DENDRITIC CELLS ; ACTIVATION ; BET ; GATA-3
收录类别	SCI
资助信息	Natural Science Foundation of China[90713033]; National 973 Basic Research Program of China[2007CB815803]; Important National Science & Technology Specific Projects[2008ZX10002-008]
语种	英语
WOS记录号	WOS:000293692500008
公开日期	2012-04-10
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/5313]
专题	昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.Shandong Univ, Inst Immunopharmacol & Immunotherapy, Sch Pharmaceut Sci, Jinan 250012, Peoples R China 2.Shandong Univ, Inst Med Chem, Sch Pharmaceut Sci, Jinan 250012, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming, Peoples R China 4.Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA 5.Ohio State Univ, Dept Chem, Columbus, OH 43210 USA 6.Univ Sci & Technol China, Dept Microbiol & Immunol, Sch Life Sci, Hefei 230026, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Zhixia,Zhang, Cai,Xia, Chengfeng,et al. Enhanced Antitumor Effects by Chemical Modified IGb3 Analogues[J]. MOLECULAR CANCER THERAPEUTICS,2011,10(8):1375-1384.
APA	Zhou, Zhixia.,Zhang, Cai.,Xia, Chengfeng.,Chen, Wenlan.,Zhu, Huawei.,...&Tian, Zhigang.(2011).Enhanced Antitumor Effects by Chemical Modified IGb3 Analogues.MOLECULAR CANCER THERAPEUTICS,10(8),1375-1384.
MLA	Zhou, Zhixia,et al."Enhanced Antitumor Effects by Chemical Modified IGb3 Analogues".MOLECULAR CANCER THERAPEUTICS 10.8(2011):1375-1384.