Blockade of B7-H1 with sPD-1 improves immunity against murine hepatocarcinoma.
BACKGROUND
The B7-H1/PD-1 pathway has been demonstrated to be involved in tumor evasion. In a previous study, we constructed a eukaryotic expression plasmid (pPD-1A), which expresses soluble PD-1 (sPD-1). In this study, the question of whether or not the blockade of B7-H1 with sPD-1 in vivo and vitro can improve antitumor immunity was investigated.


METHODS
The proliferation of lymphocytes activated by dendritic cells (DCs), which were treated with sPD-1 in vitro, was detected with MTT colorimetry. Mice inoculated with H22 cells were treated by intramuscular injection with pPD-1A. The mRNA expression was analyzed with RT-PCR.


RESULTS
The early activation of lymphocytes in vitro was partly improved by sPD-1 blockade. The growth of H22 cells was inhibited significantly after pPD-1A administration. The mRNA expression of 4-1BB, B7.1, IFN-gamma and TNF-alpha of lymphocytes was up-regulated and that of OX40 and IL-10 was down-regulated after pPD-1A administration.


CONCLUSIONS
Blockade of the PD-1/B7-H1 pathway with sPD-1 may be a promising strategy for immunotherapy for hepatocarcinoma. Both cytokines and co-stimulatory molecules of lymphocytes could be regulated by sPD-1 blockade.
He
Lanxiang
L
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Zhang
Guimei
G
He
Yufei
Y
Zhu
Hangang
H
Zhang
Hui
H
Feng
Zuohua
Z
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014162:Transfection; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C406562:OX40Ig; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma