PMID- 24236027
OWN - NLM
STAT- MEDLINE
DCOM- 20140902
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Growth differentiation factor-15 suppresses maturation and function of dendritic 
      cells and inhibits tumor-specific immune response.
PG  - e78618
LID - 10.1371/journal.pone.0078618 [doi]
LID - e78618
AB  - Dendritic cells (DCs) play a key role in the initiation stage of an 
      antigen-specific immune response. A variety of tumor-derived factors (TDFs) can 
      suppress DC maturation and function, resulting in defects in the tumor-specific 
      immune response. To identify unknown TDFs that may suppress DCs maturation and 
      function, we established a high-throughput screening technology based on a human 
      liver tumor T7 phage cDNA library and screened all of the proteins derived from 
      hepatoma cells that potentially interact with immature DCs. 
      Growth/differentiation factor-15 (GDF-15) was detected and chosen for further 
      study. By incubation of DCs cultures with GDF-15, we demonstrate that GDF-15 can 
      inhibit surface protrusion formation during DC maturation; suppress the membrane 
      expression of CD83, CD86 and HLA-DR on DCs; enhance phagocytosis by DCs; reduce 
      IL-12 and elevate TGF-beta1 secretion by DCs; inhibit T cell stimulation and 
      cytotoxic T lymphocyte (CTL) activation by DCs. By building tumor-bearing mouse 
      models, we demonstrate that GDF-15 can inhibit the ability of DCs to stimulate a 
      tumor-specific immune response in vivo. These results indicate that GDF-15 may be 
      one of the critical molecules that inhibit DC maturation and function and are 
      involved in tumor immune escape. Thus, GDF-15 may be a novel target in tumor 
      immunotherapy.
FAU - Zhou, Zhizhong
AU  - Zhou Z
AD  - The State Key Laboratory of Cancer Biology, Fourth Military Medical University, 
      Xi'an, Shaanxi, China ; Department of Biopharmaceutics, Fourth Military Medical 
      University, Xi'an, Shaanxi, China.
FAU - Li, Weina
AU  - Li W
FAU - Song, Yang
AU  - Song Y
FAU - Wang, Lili
AU  - Wang L
FAU - Zhang, Kuo
AU  - Zhang K
FAU - Yang, Jing
AU  - Yang J
FAU - Zhang, Wei
AU  - Zhang W
FAU - Su, Haichuan
AU  - Su H
FAU - Zhang, Yingqi
AU  - Zhang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131113
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (GDF15 protein, human)
RN  - 0 (Growth Differentiation Factor 15)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 187348-17-0 (Interleukin-12)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/physiology
MH  - Growth Differentiation Factor 15/*physiology
MH  - Humans
MH  - Interleukin-12/metabolism
MH  - Lymphocyte Activation
MH  - Lymphocyte Culture Test, Mixed
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neoplasm Transplantation
MH  - Phagocytosis
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transforming Growth Factor beta1/metabolism
MH  - *Tumor Escape
PMC - PMC3827235
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/16 06:00
MHDA- 2014/09/03 06:00
PMCR- 2013/11/13
CRDT- 2013/11/16 06:00
PHST- 2013/04/24 00:00 [received]
PHST- 2013/09/14 00:00 [accepted]
PHST- 2013/11/16 06:00 [entrez]
PHST- 2013/11/16 06:00 [pubmed]
PHST- 2014/09/03 06:00 [medline]
PHST- 2013/11/13 00:00 [pmc-release]
AID - PONE-D-13-16896 [pii]
AID - 10.1371/journal.pone.0078618 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 13;8(11):e78618. doi: 10.1371/journal.pone.0078618. 
      eCollection 2013.