PMID- 21717117
OWN - NLM
STAT- MEDLINE
DCOM- 20111208
LR  - 20211020
IS  - 1573-7276 (Electronic)
IS  - 0262-0898 (Linking)
VI  - 28
IP  - 7
DP  - 2011 Oct
TI  - Inhibition of T-cell responses by intratumoral hepatic stellate cells contribute 
      to migration and invasion of hepatocellular carcinoma.
PG  - 661-74
LID - 10.1007/s10585-011-9399-3 [doi]
AB  - The stroma of hepatocellular carcinoma (HCC) is markedly infiltrated with 
      activated hepatic stellate cells (HSCs), and associated invasion and metastasis 
      of HCC. However, little is known of the role of HSCs in immune responses in HCC. 
      The Buffalo rat HCC model was established. Quiescent HSCs (qHSCs) and 
      intratumoral HSCs (tHSCs) were isolated. Surface molecules of tHSC were detected 
      by flow cytometry, and gene expression was analyzed by fluorescence quantitative 
      RT-PCR. T cell proliferation was monitored by [(3)H]-thymidine ((3)H-TdR) 
      incorporation into DNA, and cytotoxic activity was assessed by measuring the 
      release of (51)Cr. The level of cytokine expression by T cells was measured by 
      enzyme-linked immunosorbent assay. T cell apoptosis was detected by 
      double-stained terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) and anti-CD3 antibodies. The migration and invasion of HCC was 
      observed by transwell experiments. tHSCs express low levels of major 
      histocompatibility complex (MHC) class I, MHC class II, and costimulatory 
      molecules, and produce varying levels of cytokines. Addition of the tHSCs 
      suppressed thymidine uptake by T cells that were stimulated by alloantigens or by 
      anti-CD3-mediated T-cell receptor ligation. The tHSC-induced T-cell 
      hyporesponsiveness was associated with enhanced T-cell apoptosis, and contributed 
      to the migration and invasion of hepatoma cell. tHSCs was associated with 
      markedly enhanced expression of B7-H1. Blockade of B7-H1/PD-1 ligation 
      significantly reduced HSC immunomodulatory activity, and hepatoma cell migration 
      and invasion. tHSCs can induce T cell apoptosis, suggesting an important role for 
      B7-H1. The interactions between tHSCs and T cells may contribute to hepatic 
      immune tolerance and invasion and migration of HCC.
FAU - Xia, Yunhong
AU  - Xia Y
AD  - Department of Oncology, Huaian Second People's Hospital, Xuzhou Medical College, 
      China.
FAU - Chen, Rongxin
AU  - Chen R
FAU - Ye, Sheng-Long
AU  - Ye SL
FAU - Sun, Ruixia
AU  - Sun R
FAU - Chen, Jun
AU  - Chen J
FAU - Zhao, Yan
AU  - Zhao Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110630
PL  - Netherlands
TA  - Clin Exp Metastasis
JT  - Clinical & experimental metastasis
JID - 8409970
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/immunology/metabolism/*pathology
MH  - *Cell Movement
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Hepatic Stellate Cells/*cytology/immunology/metabolism
MH  - Liver Neoplasms/immunology/metabolism/*pathology
MH  - Lymphocyte Activation
MH  - Neoplasm Invasiveness/*pathology
MH  - Rats
MH  - T-Lymphocytes/*cytology/immunology/metabolism
EDAT- 2011/07/01 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/07/01 06:00
PHST- 2010/12/29 00:00 [received]
PHST- 2011/06/13 00:00 [accepted]
PHST- 2011/07/01 06:00 [entrez]
PHST- 2011/07/01 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1007/s10585-011-9399-3 [doi]
PST - ppublish
SO  - Clin Exp Metastasis. 2011 Oct;28(7):661-74. doi: 10.1007/s10585-011-9399-3. Epub 
      2011 Jun 30.