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Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.

Publication ,  Journal Article
Fecci, PE; Mitchell, DA; Whitesides, JF; Xie, W; Friedman, AH; Archer, GE; Herndon, JE; Bigner, DD; Dranoff, G; Sampson, JH
Published in: Cancer Res
March 15, 2006

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.

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

March 15, 2006

Volume

66

Issue

6

Start / End Page

3294 / 3302

Location

United States

Related Subject Headings

  • Th2 Cells
  • T-Lymphocyte Subsets
  • Oncology & Carcinogenesis
  • Middle Aged
  • Lymphocyte Activation
  • Humans
  • Glioblastoma
  • Forkhead Transcription Factors
  • CD4-Positive T-Lymphocytes
  • Brain Neoplasms
 

Citation

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MLA
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Fecci, P. E., Mitchell, D. A., Whitesides, J. F., Xie, W., Friedman, A. H., Archer, G. E., … Sampson, J. H. (2006). Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res, 66(6), 3294–3302. https://doi.org/10.1158/0008-5472.CAN-05-3773
Fecci, Peter E., Duane A. Mitchell, John F. Whitesides, Weihua Xie, Allan H. Friedman, Gary E. Archer, James E. Herndon, Darell D. Bigner, Glenn Dranoff, and John H. Sampson. “Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.Cancer Res 66, no. 6 (March 15, 2006): 3294–3302. https://doi.org/10.1158/0008-5472.CAN-05-3773.
Fecci PE, Mitchell DA, Whitesides JF, Xie W, Friedman AH, Archer GE, et al. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006 Mar 15;66(6):3294–302.
Fecci, Peter E., et al. “Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.Cancer Res, vol. 66, no. 6, Mar. 2006, pp. 3294–302. Pubmed, doi:10.1158/0008-5472.CAN-05-3773.
Fecci PE, Mitchell DA, Whitesides JF, Xie W, Friedman AH, Archer GE, Herndon JE, Bigner DD, Dranoff G, Sampson JH. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006 Mar 15;66(6):3294–3302.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

March 15, 2006

Volume

66

Issue

6

Start / End Page

3294 / 3302

Location

United States

Related Subject Headings

  • Th2 Cells
  • T-Lymphocyte Subsets
  • Oncology & Carcinogenesis
  • Middle Aged
  • Lymphocyte Activation
  • Humans
  • Glioblastoma
  • Forkhead Transcription Factors
  • CD4-Positive T-Lymphocytes
  • Brain Neoplasms