PMID- 26936017
OWN - NLM
STAT- MEDLINE
DCOM- 20161228
LR  - 20161230
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 13
IP  - 4
DP  - 2016 Apr
TI  - Improvement of the cytotoxic T lymphocyte response against hepatocellular 
      carcinoma by transduction of cancer cells with an adeno-associated virus carrying 
      the interferon-gamma gene.
PG  - 3197-205
LID - 10.3892/mmr.2016.4884 [doi]
AB  - Dendritic cell (DC)-based antigen-targeted immunotherapy may offer effective 
      adjuvant therapy for hepatocellular carcinoma (HCC), in which cytotoxic T 
      lymphocytes (CTLs) are key. However, in a number of cases, the activity of CTLs 
      is completely inhibited due to the downregulated expression of major human 
      leukocyte antigen (HLA) class I molecules by HCC cells. The aim of the present 
      study was to overcome this issue. Hep3B cells were transduced by HCC‑specific 
      recombinant adeno‑associated virus (rAAV) carrying human alpha‑fetoprotein promoter 
      (AFPp) and the interferon‑gamma (IFN‑gamma) gene (rAAV/AFPp‑IFN‑gamma). rAAV carrying the 
      cytomegalovirus promoter (CMVp) and human alpha‑fetoprotein (AFP) gene 
      (rAAV/CMVp‑AFP) was used to transduce professional antigen‑presenting DCs for the 
      purpose of stimulating a CTL response. It was observed that transduction of DCs 
      with rAAV/CMVp‑AFP resulted in: (i) AFP and interleukin‑12 expression; (ii) high 
      expression levels of cluster of differentiation (CD)80, CD83, CD86, CD40, 
      HLA‑death receptor and CD1a; (iii) T cell populations with marked IFN‑gamma 
      expression; (iv) a high percentage of CD69+/CD8+ T cells; and (v) the activity of 
      CTLs against HLA‑A2‑expressing Hep3B cells. The transduction of Hep3B cells with 
      rAAV/AFPp‑IFN‑gamma resulted in: (i) IFN‑gamma expression; (ii) upregulated expression of 
      HLA‑A2; and (iii) an improved CTL response against HLA‑A2‑deficient Hep3B cells. 
      rAAV/CMVp‑AFP‑transduced DCs elicited an AFP‑specific and HLA‑class I‑restricted 
      CTL response against Hep3B cells. In conclusion, it was shown that the 
      transduction of Hep3B with rAAV/AFPp-IFN-gamma upregulated the expression of HLA-A2 
      and improved the sensitivity to CTL response.
FAU - Zhou, Jun
AU  - Zhou J
AD  - Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, Shandong 250021, P.R. China.
FAU - Ma, Ping
AU  - Ma P
AD  - Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, Shandong 250021, P.R. China.
FAU - Li, Jun
AU  - Li J
AD  - Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, Shandong 250021, P.R. China.
FAU - Cui, Xiaonan
AU  - Cui X
AD  - Department of Oncology, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning 116011, P.R. China.
FAU - Song, Wei
AU  - Song W
AD  - Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong 
      University, Jinan, Shandong 250021, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160210
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (AFP protein, human)
RN  - 0 (Antigens, CD)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (alpha-Fetoproteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Carcinoma, Hepatocellular/immunology/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/cytology/immunology
MH  - Dependovirus/*genetics
MH  - Genetic Vectors/genetics/*metabolism
MH  - HLA-A2 Antigen/metabolism
MH  - Humans
MH  - Interferon-gamma/genetics/*metabolism
MH  - Liver Neoplasms/immunology/metabolism/pathology
MH  - Lymphocyte Activation
MH  - Promoter Regions, Genetic
MH  - T-Lymphocytes, Cytotoxic/cytology/immunology/*metabolism
MH  - Transduction, Genetic
MH  - Up-Regulation
MH  - alpha-Fetoproteins/genetics
EDAT- 2016/03/05 06:00
MHDA- 2016/12/29 06:00
CRDT- 2016/03/04 06:00
PHST- 2015/03/06 00:00 [received]
PHST- 2015/12/11 00:00 [accepted]
PHST- 2016/03/04 06:00 [entrez]
PHST- 2016/03/05 06:00 [pubmed]
PHST- 2016/12/29 06:00 [medline]
AID - 10.3892/mmr.2016.4884 [doi]
PST - ppublish
SO  - Mol Med Rep. 2016 Apr;13(4):3197-205. doi: 10.3892/mmr.2016.4884. Epub 2016 Feb 
      10.