PMID- 16540683
OWN - NLM
STAT- MEDLINE
DCOM- 20060503
LR  - 20230413
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 6
DP  - 2006 Mar 15
TI  - Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains 
      cellular immune defects in patients with malignant glioma.
PG  - 3294-302
AB  - Immunosuppression is frequently associated with malignancy and is particularly 
      severe in patients with malignant glioma. Anergy and counterproductive shifts 
      toward T(H)2 cytokine production are long-recognized T-cell defects in these 
      patients whose etiology has remained elusive for >30 years. We show here that 
      absolute counts of both CD4(+) T cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+) T cells 
      (T(regs)) are greatly diminished in patients with malignant glioma, but T(regs) 
      frequently represent an increased fraction of the remaining CD4 compartment. This 
      increased T(reg) fraction, despite reduced counts, correlates with and is 
      sufficient to elicit the characteristic manifestations of impaired patient T-cell 
      responsiveness in vitro. Furthermore, T(reg) removal eradicates T-cell 
      proliferative defects and reverses T(H)2 cytokine shifts, allowing T cells from 
      patients with malignant glioma to function in vitro at levels equivalent to those 
      of normal, healthy controls. Such restored immune function may give license to 
      physiologic antiglioma activity, as in vivo, T(reg) depletion proves permissive 
      for spontaneous tumor rejection in a murine model of established intracranial 
      glioma. These findings dramatically alter our understanding of depressed cellular 
      immune function in patients with malignant glioma and advance a role for T(regs) 
      in facilitating tumor immune evasion in the central nervous system.
FAU - Fecci, Peter E
AU  - Fecci PE
AD  - Division of Neurosurgery, Department of Surgery, Duke University Medical Center, 
      Durham, North Carolina 27710, USA.
FAU - Mitchell, Duane A
AU  - Mitchell DA
FAU - Whitesides, John F
AU  - Whitesides JF
FAU - Xie, Weihua
AU  - Xie W
FAU - Friedman, Allan H
AU  - Friedman AH
FAU - Archer, Gary E
AU  - Archer GE
FAU - Herndon, James E 2nd
AU  - Herndon JE 2nd
FAU - Bigner, Darell D
AU  - Bigner DD
FAU - Dranoff, Glenn
AU  - Dranoff G
FAU - Sampson, John H
AU  - Sampson JH
LA  - eng
GR  - 1P50 CA108786/CA/NCI NIH HHS/United States
GR  - R01 CA09722/CA/NCI NIH HHS/United States
GR  - T32 GM-07171/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Brain Neoplasms/blood/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Forkhead Transcription Factors/immunology
MH  - Glioblastoma/blood/*immunology
MH  - Humans
MH  - Lymphocyte Activation
MH  - Middle Aged
MH  - T-Lymphocyte Subsets/*immunology
MH  - Th2 Cells/immunology
EDAT- 2006/03/17 09:00
MHDA- 2006/05/04 09:00
CRDT- 2006/03/17 09:00
PHST- 2006/03/17 09:00 [pubmed]
PHST- 2006/05/04 09:00 [medline]
PHST- 2006/03/17 09:00 [entrez]
AID - 66/6/3294 [pii]
AID - 10.1158/0008-5472.CAN-05-3773 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Mar 15;66(6):3294-302. doi: 10.1158/0008-5472.CAN-05-3773.