PMID- 21908444
OWN - NLM
STAT- MEDLINE
DCOM- 20120320
LR  - 20240417
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 13
IP  - 12
DP  - 2011 Dec
TI  - Thymus-derived rather than tumor-induced regulatory T cells predominate in brain 
      tumors.
PG  - 1308-23
LID - 10.1093/neuonc/nor134 [doi]
AB  - Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an average 
      survival time of 15 months. Previously, we and others demonstrated that 
      CD4(+)FoxP3(+) regulatory T cells (Tregs) infiltrate human GBM as well as mouse 
      models that recapitulate malignant brain tumors. However, whether brain 
      tumor-resident Tregs are thymus-derived natural Tregs (nTregs) or induced Tregs 
      (iTregs), by the conversion of conventional CD4(+) T cells, has not been 
      established. To investigate this question, we utilized the i.c. implanted GL261 
      cell-based orthotopic mouse model, the RasB8 transgenic astrocytoma mouse model, 
      and a human GBM tissue microarray. We demonstrate that Tregs in brain tumors are 
      predominantly thymus derived, since thymectomy, prior to i.c. GL261 cell 
      implantation, significantly decreased the level of Tregs in mice with brain 
      tumors. Accordingly, most Tregs in human GBM and mouse brain tumors expressed the 
      nTreg transcription factor, Helios. Interestingly, a significant effect of the 
      brain tumor microenvironment on Treg lineage programming was observed, based on 
      higher levels of brain tumor-resident Tregs expressing glucocorticoid-induced 
      tumor necrosis factor receptor and CD103 and lower levels of Tregs expressing 
      CD62L and CD45RB compared with peripheral Tregs. Furthermore, there was a higher 
      level of nTregs in brain tumors that expressed the proliferative marker Ki67 
      compared with iTregs and conventional CD4(+) T cells. Our study demonstrates that 
      future Treg-depleting therapies should aim to selectively target systemic rather 
      than intratumoral nTregs in brain tumor-specific immunotherapeutic strategies.
FAU - Wainwright, Derek A
AU  - Wainwright DA
AD  - The Brain Tumor Center, The University of Chicago, 5841 S. Maryland Ave, MC 3026, 
      Chicago, IL 60637, USA.
FAU - Sengupta, Sadhak
AU  - Sengupta S
FAU - Han, Yu
AU  - Han Y
FAU - Lesniak, Maciej S
AU  - Lesniak MS
LA  - eng
GR  - F32 NS073366/NS/NINDS NIH HHS/United States
GR  - R00 NS082381/NS/NINDS NIH HHS/United States
GR  - F32 NS073366-01A1/NS/NINDS NIH HHS/United States
GR  - R01CA138587/CA/NCI NIH HHS/United States
GR  - K99 NS082381/NS/NINDS NIH HHS/United States
GR  - F32NS073366/NS/NINDS NIH HHS/United States
GR  - R01 CA138587-03/CA/NCI NIH HHS/United States
GR  - R01 CA138587/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110908
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Biomarkers, Tumor)
SB  - IM
CIN - Neuro Oncol. 2011 Dec;13(12):1261. PMID: 22113488
MH  - Animals
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Brain Neoplasms/*immunology/metabolism/mortality
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Profiling
MH  - Glioblastoma/*immunology/metabolism/mortality
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/*immunology/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Oligonucleotide Array Sequence Analysis
MH  - Survival Rate
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism/pathology
MH  - Thymectomy
MH  - Thymus Gland/cytology/*immunology/metabolism
PMC - PMC3223094
EDAT- 2011/09/13 06:00
MHDA- 2012/03/21 06:00
PMCR- 2012/12/01
CRDT- 2011/09/13 06:00
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/03/21 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - nor134 [pii]
AID - 10.1093/neuonc/nor134 [doi]
PST - ppublish
SO  - Neuro Oncol. 2011 Dec;13(12):1308-23. doi: 10.1093/neuonc/nor134. Epub 2011 Sep 
      8.