EBV-Induced Human CD8(+) NKT Cells Suppress Tumorigenesis by EBV-Associated Malignancies

	EBV-Induced Human CD8(+) NKT Cells Suppress Tumorigenesis by EBV-Associated Malignancies
	He, YL; Xiao, RJ; Li, L; Ji, X; Zhou, R; Wang, YJ; Zhang, LJ; Du, CX; Tan, XT; Xiao, W
刊名	CANCER RESEARCH
	2009
卷号	69 期号:20 页码:7935-7944
通讯作者	Tan, JQ (reprint author), Wuhan Univ, Sch Med, Dept Immunol, Dong Hu Rd 115, Wuhan 430071, Peoples R China.,jinquan_tan@whu.edu.cn
英文摘要	The underlying mechanism of the protective and suppressive role of NKT cells in human tumor immunosurveillance remains to be fully elucidated. We show that the frequencies of CD8(+) NKT cells in patients with EBV-associated Hodgkin's lymphoma or nasopharyngeal carcinoma are significantly lower than those in healthy EBV carriers. These CD8(+) NKT cells in tumor patients are also functionally impaired. In human-thymus-severe combined immunodeficient (hu-thym-SCID) chimeras, EBV challenge efficiently promotes the generation of IFN-gamma-biased CD8(+) NKT cells. These cells are strongly cytotoxic, drive syngeneic T cells into a Th1 bias, and enhance T-cell cytotoxicity to EBV-associated tumor cells. Interleukin-4-biased CD4(+) NKT cells are predominately generated in unchallenged chimeras. These cells are noncytotoxic, drive syngeneic T cells into a Th2 bias, and do not affect T-cell cytotoxicity. In humanized xenogeneic tumor-transplanted hu-thym-SCID chimeras, adoptive transfer with EBV-induce CD8(+) NKT cells significantly suppresses tumorigenesis by EBV-associated malignancies. EBV-induced CD8(+) NKT cells are necessary and sufficient to enhance the T-cell immunity to EBV-associated malignancies in the hu-thym-SCID chimeras. CD4(+) NKT cells are synergetic with CD8(+) NKT cells, leading to a more pronounced T-cell antitumor response in the chimeras cotransferred with CD4(+) and CD8(+) NKT cells. Thus, immune reconstitution with EBV-induced CD8(+) NKT cells could be a useful strategy in management of EBV-associated malignancies. [Cancer Res 2009;69(20):7935-44]
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	EPSTEIN-BARR-VIRUS ; KILLER T-CELLS ; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISEASE ; NATURAL-KILLER ; TUMOR IMMUNOSURVEILLANCE ; NASOPHARYNGEAL CARCINOMA ; HODGKIN LYMPHOMA ; IMMUNOREGULATORY AXIS ; SECONDARY EXPANSION ; DENDRITIC CELLS
收录类别	SCI
语种	英语
WOS记录号	WOS:000270935500007
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1282]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	He, YL,Xiao, RJ,Li, L,et al. EBV-Induced Human CD8(+) NKT Cells Suppress Tumorigenesis by EBV-Associated Malignancies[J]. CANCER RESEARCH,2009,69(20):7935-7944.
APA	He, YL.,Xiao, RJ.,Li, L.,Ji, X.,Zhou, R.,...&Tan, JQ.(2009).EBV-Induced Human CD8(+) NKT Cells Suppress Tumorigenesis by EBV-Associated Malignancies.CANCER RESEARCH,69(20),7935-7944.
MLA	He, YL,et al."EBV-Induced Human CD8(+) NKT Cells Suppress Tumorigenesis by EBV-Associated Malignancies".CANCER RESEARCH 69.20(2009):7935-7944.