PMID- 25753156
OWN - NLM
STAT- MEDLINE
DCOM- 20150824
LR  - 20220310
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 181
IP  - 1
DP  - 2015 Jul
TI  - The siRNA cocktail targeting interleukin 10 receptor and transforming growth 
      factor-beta receptor on dendritic cells potentiates tumour antigen-specific CD8(+) T 
      cell immunity.
PG  - 164-78
LID - 10.1111/cei.12620 [doi]
AB  - Dendritic cells (DCs) are promising therapeutic agents in the field of cancer 
      immunotherapy due to their intrinsic immune-priming capacity. The potency of DCs, 
      however, is readily attenuated immediately after their administration in patients 
      as tumours and various immune cells, including DCs, produce various 
      immunosuppressive factors such as interleukin (IL)-10 and transforming growth 
      factor (TGF)-beta that hamper the function of DCs. In this study, we used small 
      interfering RNA (siRNA) to silence the expression of endogenous molecules in DCs, 
      which can sense immunosuppressive factors. Among the siRNAs targeting various 
      immunosuppressive molecules, we observed that DCs transfected with siRNA 
      targeting IL-10 receptor alpha (siIL-10RA) initiated the strongest 
      antigen-specific CD8(+) T cell immune responses. The potency of siIL-10RA was 
      enhanced further by combining it with siRNA targeting TGF-beta receptor (siTGF-betaR), 
      which was the next best option during the screening of this study, or the 
      previously selected immunoadjuvant siRNA targeting phosphatase and tensin 
      homologue deleted on chromosome 10 (PTEN) or Bcl-2-like protein 11 (BIM). In the 
      midst of sorting out the siRNA cocktails, the cocktail of siIL-10RA and siTGF-betaR 
      generated the strongest antigen-specific CD8(+) T cell immunity. Concordantly, 
      the knock-down of both IL-10RA and TGF-betaR in DCs induced the strongest 
      anti-tumour effects in the TC-1 P0 tumour model, a cervical cancer model 
      expressing the human papillomavirus (HPV)-16 E7 antigen, and even in the 
      immune-resistant TC-1 (P3) tumour model that secretes more IL-10 and TGF-beta than 
      the parental tumour cells (TC-1 P0). These results provide the groundwork for 
      future clinical development of the siRNA cocktail-mediated strategy by 
      co-targeting immunosuppressive molecules to enhance the potency of DC-based 
      vaccines.
CI  - (c) 2015 British Society for Immunology.
FAU - Ahn, Y-H
AU  - Ahn YH
AD  - Division of Infection and Immunology, Graduate School of Medicine, Korea 
      University.
AD  - Department of Biochemistry and Molecular Biology, Korea University College of 
      Medicine, Seoul, Korea.
FAU - Hong, S-O
AU  - Hong SO
AD  - Division of Infection and Immunology, Graduate School of Medicine, Korea 
      University.
AD  - Department of Biochemistry and Molecular Biology, Korea University College of 
      Medicine, Seoul, Korea.
FAU - Kim, J H
AU  - Kim JH
AD  - Division of Infection and Immunology, Graduate School of Medicine, Korea 
      University.
AD  - Department of Biochemistry and Molecular Biology, Korea University College of 
      Medicine, Seoul, Korea.
FAU - Noh, K H
AU  - Noh KH
AD  - Division of Infection and Immunology, Graduate School of Medicine, Korea 
      University.
AD  - Department of Biochemistry and Molecular Biology, Korea University College of 
      Medicine, Seoul, Korea.
AD  - Department of Gynecologic Oncology and Reproductive Medicine, University of Texas 
      M. D. Anderson Cancer Center, Houston, TX, USA.
FAU - Song, K-H
AU  - Song KH
AD  - Division of Infection and Immunology, Graduate School of Medicine, Korea 
      University.
AD  - Department of Biochemistry and Molecular Biology, Korea University College of 
      Medicine, Seoul, Korea.
FAU - Lee, Y-H
AU  - Lee YH
AD  - Division of Infection and Immunology, Graduate School of Medicine, Korea 
      University.
AD  - Department of Biochemistry and Molecular Biology, Korea University College of 
      Medicine, Seoul, Korea.
FAU - Jeon, J-H
AU  - Jeon JH
AD  - Department of Physiology.
FAU - Kim, D-W
AU  - Kim DW
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Korea.
FAU - Seo, J H
AU  - Seo JH
AD  - Division of Oncology, Department of Internal Medicine, College of Medicine, Korea 
      University, Seoul, Korea.
FAU - Kim, T W
AU  - Kim TW
AD  - Division of Infection and Immunology, Graduate School of Medicine, Korea 
      University.
AD  - Department of Biochemistry and Molecular Biology, Korea University College of 
      Medicine, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150517
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BCL2L11 protein, human)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Bcl2l11 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Interleukin-10)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/immunology
MH  - Apoptosis Regulatory Proteins/genetics
MH  - Bcl-2-Like Protein 11
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Human papillomavirus 16
MH  - Immunotherapy/methods
MH  - Lymphocyte Activation/immunology
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - PTEN Phosphohydrolase/genetics
MH  - Papillomavirus E7 Proteins/metabolism
MH  - Proto-Oncogene Proteins/genetics
MH  - RNA Interference
MH  - RNA, Small Interfering/*pharmacology
MH  - Receptors, Interleukin-10/*genetics
MH  - Transforming Growth Factor beta/*genetics
MH  - Uterine Cervical Neoplasms/immunology/therapy/virology
PMC - PMC4469167
OTO - NOTNLM
OT  - IL-10RA
OT  - TGF-beta
OT  - dendritic cell
OT  - immunotherapy
OT  - siRNA
EDAT- 2015/03/11 06:00
MHDA- 2015/08/25 06:00
PMCR- 2016/07/01
CRDT- 2015/03/11 06:00
PHST- 2015/03/02 00:00 [accepted]
PHST- 2015/03/11 06:00 [entrez]
PHST- 2015/03/11 06:00 [pubmed]
PHST- 2015/08/25 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - 10.1111/cei.12620 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2015 Jul;181(1):164-78. doi: 10.1111/cei.12620. Epub 2015 May 
      17.