PMID- 23300824
OWN - NLM
STAT- MEDLINE
DCOM- 20130624
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - TNF-alpha and tumor lysate promote the maturation of dendritic cells for 
      immunotherapy for advanced malignant bone and soft tissue tumors.
PG  - e52926
LID - 10.1371/journal.pone.0052926 [doi]
LID - e52926
AB  - BACKGROUND: Dendritic cells (DCs) play a pivotal role in the immune system. There 
      are many reports concerning DC-based immunotherapy. The differentiation and 
      maturation of DCs is a critical part of DC-based immunotherapy. We investigated 
      the differentiation and maturation of DCs in response to various stimuli. 
      METHODS: Thirty-one patients with malignant bone and soft tissue tumors were 
      enrolled in this study. All the patients had metastatic tumors and/or recurrent 
      tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media 
      containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating 
      factor (GM-CSF). These cells were then treated with or without 1) tumor lysate 
      (TL), 2) TL + TNF-alpha, 3) OK-432. The generated DCs were mixed and injected in the 
      inguinal or axillary region. Treatment courses were performed every week and 
      repeated 6 times. A portion of the cells were analyzed by flow cytometry to 
      determine the degree of differentiation and maturation of the DCs. Serum IFN-gamma 
      and serum IL-12 were measured in order to determine the immune response following 
      the DC-based immunotherapy. RESULTS: Approximately 50% of PBMCs differentiated 
      into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation 
      of the TL/TNF-alpha-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. 
      Serum IFN-gamma and serum IL-12 showed significant elevation at one and three months 
      after DC-based immunotherapy. CONCLUSIONS: Although TL-pulsed DCs exhibit tumor 
      specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, 
      the TL/TNF-alpha-pulsed DCs showed remarkable maturation. The combination of 
      IL-4/GM-CSF/TL/TNF-alpha resulted in the greatest differentiation and maturation for 
      DC-based immunotherapy for patients with bone and soft tissue tumors.
FAU - Miwa, Shinji
AU  - Miwa S
AD  - Department of Orthopaedic Surgery, Kanazawa University School of Medicine, 
      Kanazawa, Japan.
FAU - Nishida, Hideji
AU  - Nishida H
FAU - Tanzawa, Yoshikazu
AU  - Tanzawa Y
FAU - Takata, Munetomo
AU  - Takata M
FAU - Takeuchi, Akihiko
AU  - Takeuchi A
FAU - Yamamoto, Norio
AU  - Yamamoto N
FAU - Shirai, Toshiharu
AU  - Shirai T
FAU - Hayashi, Katsuhiro
AU  - Hayashi K
FAU - Kimura, Hiroaki
AU  - Kimura H
FAU - Igarashi, Kentaro
AU  - Igarashi K
FAU - Mizukoshi, Eishiro
AU  - Mizukoshi E
FAU - Nakamoto, Yasunari
AU  - Nakamoto Y
FAU - Kaneko, Shuichi
AU  - Kaneko S
FAU - Tsuchiya, Hiroyuki
AU  - Tsuchiya H
LA  - eng
PT  - Journal Article
DEP - 20121221
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - 207137-56-2 (Interleukin-4)
RN  - 39325-01-4 (Picibanil)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
EIN - PLoS One. 2013;8(10). doi:10.1371/annotation/7c0f14e6-cfba-4f5f-b93d-1a149eaeec96
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Bone Neoplasms/drug therapy/immunology/*therapy
MH  - Cell Differentiation
MH  - Child
MH  - Dendritic Cells/*drug effects/immunology
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology/therapeutic use
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Interleukin-12/pharmacology/therapeutic use
MH  - Interleukin-4/pharmacology/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Picibanil/pharmacology/therapeutic use
MH  - Soft Tissue Neoplasms/drug therapy/immunology/*therapy
MH  - Tumor Necrosis Factor-alpha/pharmacology/*therapeutic use
PMC - PMC3533902
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/10 06:00
MHDA- 2013/06/26 06:00
PMCR- 2012/12/21
CRDT- 2013/01/10 06:00
PHST- 2012/05/14 00:00 [received]
PHST- 2012/11/22 00:00 [accepted]
PHST- 2013/01/10 06:00 [entrez]
PHST- 2013/01/10 06:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
PHST- 2012/12/21 00:00 [pmc-release]
AID - PONE-D-12-13753 [pii]
AID - 10.1371/journal.pone.0052926 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e52926. doi: 10.1371/journal.pone.0052926. Epub 2012 Dec 21.