PMID- 26967393
OWN - NLM
STAT- MEDLINE
DCOM- 20180124
LR  - 20221202
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 15
DP  - 2016 Apr 12
TI  - Loss of SOCS3 in myeloid cells prolongs survival in a syngeneic model of glioma.
PG  - 20621-35
LID - 10.18632/oncotarget.7992 [doi]
AB  - In glioma, microglia and macrophages are the largest population of 
      tumor-infiltrating cells, referred to as glioma associated macrophages (GAMs). 
      Herein, we sought to determine the role of Suppressor of Cytokine Signaling 3 
      (SOCS3), a negative regulator of Signal Transducer and Activator of Transcription 
      3 (STAT3), in GAM functionality in glioma. We utilized a conditional model in 
      which SOCS3 deletion is restricted to the myeloid cell population. We found that 
      SOCS3-deficient bone marrow-derived macrophages display enhanced and prolonged 
      expression of pro-inflammatory M1 cytokines when exposed to glioma tumor cell 
      conditioned medium in vitro. Moreover, we found that deletion of SOCS3 in the 
      myeloid cell population delays intracranial tumor growth and increases survival 
      of mice bearing orthotopic glioma tumors in vivo. Although intracranial tumors 
      from mice with SOCS3-deficient myeloid cells appear histologically similar to 
      control mice, we observed that loss of SOCS3 in myeloid cells results in 
      decreased M2 polarized macrophage infiltration in the tumors. Furthermore, loss 
      of SOCS3 in myeloid cells results in increased CD8+ T-cell and decreased 
      regulatory T-cell infiltration in the tumors. These findings demonstrate a 
      beneficial effect of M1 polarized macrophages on suppressing glioma tumor growth, 
      and highlight the importance of immune cells in the tumor microenvironment.
FAU - McFarland, Braden C
AU  - McFarland BC
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, USA.
FAU - Marks, Margaret P
AU  - Marks MP
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, USA.
FAU - Rowse, Amber L
AU  - Rowse AL
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, USA.
FAU - Fehling, Samuel C
AU  - Fehling SC
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, USA.
FAU - Gerigk, Magda
AU  - Gerigk M
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, USA.
FAU - Qin, Hongwei
AU  - Qin H
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, USA.
FAU - Benveniste, Etty N
AU  - Benveniste EN
AD  - Department of Cell, Developmental and Integrative Biology, University of Alabama 
      at Birmingham, Birmingham, AL, USA.
LA  - eng
GR  - P30 NS047466/NS/NINDS NIH HHS/United States
GR  - R01 CA158534/CA/NCI NIH HHS/United States
GR  - P30 AR048311/AR/NIAMS NIH HHS/United States
GR  - R25 CA076023/CA/NCI NIH HHS/United States
GR  - R01 NS057563/NS/NINDS NIH HHS/United States
GR  - R01 CA194414/CA/NCI NIH HHS/United States
GR  - P01 CA071933/CA/NCI NIH HHS/United States
GR  - T32 NS048039/NS/NINDS NIH HHS/United States
GR  - P30 CA013148/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Brain Neoplasms/genetics/immunology/*pathology
MH  - Cell Proliferation
MH  - Glioma/genetics/immunology/*pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Myeloid Cells/immunology/metabolism/*pathology
MH  - Suppressor of Cytokine Signaling 3 Protein/*physiology
MH  - T-Lymphocytes, Regulatory/immunology/metabolism/*pathology
MH  - Tumor Cells, Cultured
MH  - Tumor Microenvironment/immunology
PMC - PMC4991480
OTO - NOTNLM
OT  - GL261
OT  - JAK/STAT
OT  - SOCS3
OT  - glioblastoma
OT  - macrophage
COIS- CONFLICTS OF INTEREST The authors declare no financial or competing conflicts of 
      interests.
EDAT- 2016/03/12 06:00
MHDA- 2018/01/25 06:00
PMCR- 2016/04/12
CRDT- 2016/03/12 06:00
PHST- 2016/09/14 00:00 [received]
PHST- 2016/02/16 00:00 [accepted]
PHST- 2016/03/12 06:00 [entrez]
PHST- 2016/03/12 06:00 [pubmed]
PHST- 2018/01/25 06:00 [medline]
PHST- 2016/04/12 00:00 [pmc-release]
AID - 7992 [pii]
AID - 10.18632/oncotarget.7992 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Apr 12;7(15):20621-35. doi: 10.18632/oncotarget.7992.