Dendritic cells-mediated CTLs targeting hepatocellular carcinoma stem cells.
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.
Sun
Jian-cong
JC
State Key Laboratory of Oncology in South China, Guangzhou, China.
Pan
Ke
K
Chen
Min-shan
MS
Wang
Qi-jing
QJ
Wang
Hui
H
Ma
Hai-qing
HQ
Li
Yong-qiang
YQ
Liang
Xiao-ting
XT
Li
Jian-jun
JJ
Zhao
Jing-jing
JJ
Chen
Yi-bing
YB
Pang
Xiong-hao
XH
Liu
Wang-li
WL
Cao
Yun
Y
Guan
Xin-yuan
XY
Lian
Qi-zhou
QZ
Xia
Jian-chuan
JC
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*
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