PMID- 24690994
OWN - NLM
STAT- MEDLINE
DCOM- 20150119
LR  - 20240502
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 15
IP  - 4
DP  - 2014 Mar 31
TI  - Transgene IL-6 enhances DC-stimulated CTL responses by counteracting 
      CD4+25+Foxp3+ regulatory T cell suppression via IL-6-induced Foxp3 
      downregulation.
PG  - 5508-21
LID - 10.3390/ijms15045508 [doi]
AB  - Dendritic cells (DCs), the most potent antigen-presenting cells have been 
      extensively applied in clinical trials for evaluation of antitumor immunity. 
      However, the efficacy of DC-mediated cancer vaccines is still limited as they are 
      unable to sufficiently break the immune tolerance. In this study, we constructed 
      a recombinant adenoviral vector (AdVIL-6) expressing IL-6, and generated IL-6 
      transgene-engineered DC vaccine (DCOVA/IL-6) by transfection of murine bone 
      marrow-derived ovalbumin (OVA)-pulsed DCs (DCOVA) with AdVIL-6. We then assessed 
      DCOVA/IL-6-stimulated cytotoxic T-lymphocyte (CTL) responses and antitumor 
      immunity in OVA-specific animal tumor model. We demonstrate that DCOVA/IL-6 
      vaccine up-regulates expression of DC maturation markers, secretes 
      transgene-encoded IL-6, and more efficiently stimulates OVA-specific CTL 
      responses and therapeutic immunity against OVA-expressing B16 melanoma BL6-10OVA 
      in vivo than the control DCOVA/Null vaccine. Moreover, DCOVA/IL-6-stimulated CTL 
      responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ 
      Tr-cells, but significantly reduced when treated with anti-IL-6 antibody. In 
      addition, we demonstrate that IL-6 down-regulates Foxp3-expression of 
      CD4+25+Foxp3+ Tr-cells in vitro. Taken together, our results demonstrate that 
      AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses 
      and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via 
      IL-6-induced Foxp3 down-regulation. Thus, IL-6 may be a good candidate for 
      engineering DCs for cancer immunotherapy.
FAU - Bhanumathy, Kalpana Kalyanasundaram
AU  - Bhanumathy KK
AD  - Cancer Research Unit, Saskatchewan Cancer Agency, Saskatoon, SK S7N 5E5, Canada. 
      kak677@mail.usask.ca.
FAU - Zhang, Bei
AU  - Zhang B
AD  - Cancer Research Unit, Saskatchewan Cancer Agency, Saskatoon, SK S7N 5E5, Canada. 
      bei.zhang@usask.ca.
FAU - Ahmed, Khawaja Ashfaque
AU  - Ahmed KA
AD  - Cancer Research Unit, Saskatchewan Cancer Agency, Saskatoon, SK S7N 5E5, Canada. 
      kaa201@mail.usask.ca.
FAU - Qureshi, Mabood
AU  - Qureshi M
AD  - Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK S7N 
      5E5, Canada. mabood.qureshi@saskatoonhealthregion.ca.
FAU - Xie, Yufeng
AU  - Xie Y
AD  - Department of Oncology, the First Affiliated Hospital of Soochow University, 
      Soochow 215000, China. sdxyf@163.com.
FAU - Tao, Min
AU  - Tao M
AD  - Department of Oncology, the First Affiliated Hospital of Soochow University, 
      Soochow 215000, China. mtao@medmail.com.cn.
FAU - Tan, Xin
AU  - Tan X
AD  - School of Life Sciences, Beijing Institute of Technology, Beijing 100081, China. 
      tanxing@bit.edu.cn.
FAU - Xiang, Jim
AU  - Xiang J
AD  - Cancer Research Unit, Saskatchewan Cancer Agency, Saskatoon, SK S7N 5E5, Canada. 
      jim.xiang@usask.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140331
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CD4 Antigens)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Interleukin-6)
RN  - 0 (Vaccines, Synthetic)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - CD4 Antigens/immunology
MH  - Cancer Vaccines/chemical synthesis/genetics/*immunology
MH  - Cell Line, Tumor
MH  - Cloning, Molecular
MH  - Dendritic Cells/*immunology
MH  - Down-Regulation
MH  - Forkhead Transcription Factors/biosynthesis/immunology
MH  - Interleukin-2 Receptor alpha Subunit/immunology
MH  - Interleukin-6/*genetics
MH  - Melanoma, Experimental/*immunology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovalbumin/immunology
MH  - Signal Transduction/genetics/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Transfection/methods
MH  - Vaccination
MH  - Vaccines, Synthetic
PMC - PMC4013578
EDAT- 2014/04/03 06:00
MHDA- 2015/01/20 06:00
PMCR- 2014/04/01
CRDT- 2014/04/03 06:00
PHST- 2013/12/24 00:00 [received]
PHST- 2014/02/25 00:00 [revised]
PHST- 2014/03/06 00:00 [accepted]
PHST- 2014/04/03 06:00 [entrez]
PHST- 2014/04/03 06:00 [pubmed]
PHST- 2015/01/20 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - ijms15045508 [pii]
AID - ijms-15-05508 [pii]
AID - 10.3390/ijms15045508 [doi]
PST - epublish
SO  - Int J Mol Sci. 2014 Mar 31;15(4):5508-21. doi: 10.3390/ijms15045508.