title: Dendritic cells-mediated CTLs targeting hepatocellular carcinoma stem cells.
abstract: Immunotherapy, especially using dendritic cells (DCs)-based vaccine, appears promising in the treatment of hepatocellular carcinoma (HCC) following surgery. However, the therapeutic efficacy of current DC vaccines loaded with HCC antigen is limited in clinical practice. One important reason might be that the DC vaccines for the treatment of HCC were not aimed at targeting the hepatocellular carcinoma cancer stem cells (HCCCSCs). Therefore, establishing an immunotherapy to kill HCC stem cells could be a novel therapeutic strategy. In this study, we have developed an immunotherapy to target CD133(+) HCC cells in the treatment of HCC. This study had three main findings; (1) CD133(+)HCC cells RNA loaded DCs could induce special CD8(+) cytotoxic T lymphocytes (CD133(+)Huh7-CTLs) response against CD133(+) Huh7 cells in vitro. (2) Huh7 cells-induced tumor growth in vivo was effectively inhibited by CD133(+)Huh7-CTLs. (3) the great inhibition potential of CD133(+)Huh7-CTLs to Huh7-induced tumor growth might not be only associated with anti-tumor cytokines such as IFNγ, but also to CD133(+)Huh7-DCs induced specific CTLs. This study shows an experimental proof that CD133(+)HCC cells RNA loaded DC vaccine has potential in treating HCC and may provide a new therapy for clinical post operative adjuvant therapy in future.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: Jian-cong
authors.initials: JC
authors.lastname: Sun
authors.forename: Ke
authors.initials: K
authors.lastname: Pan
authors.forename: Min-shan
authors.initials: MS
authors.lastname: Chen
authors.forename: Qi-jing
authors.initials: QJ
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Hai-qing
authors.initials: HQ
authors.lastname: Ma
authors.forename: Yong-qiang
authors.initials: YQ
authors.lastname: Li
authors.forename: Xiao-ting
authors.initials: XT
authors.lastname: Liang
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Yi-bing
authors.initials: YB
authors.lastname: Chen
authors.forename: Xiong-hao
authors.initials: XH
authors.lastname: Pang
authors.forename: Wang-li
authors.initials: WL
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Cao
authors.forename: Xin-yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Qi-zhou
authors.initials: QZ
authors.lastname: Lian
authors.forename: Jian-chuan
authors.initials: JC
authors.lastname: Xia
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D015870:Gene Expression; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D012313:RNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D019496:Cancer Vaccines; D006023:Glycoproteins; D015851:Interleukin-7; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D018664:Interleukin-12; D012313:RNA; D007371:Interferon-gamma