Increased proportion of FoxP3+ regulatory T cells in tumor infiltrating lymphocytes is associated with tumor recurrence and reduced survival in patients with glioblastoma

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• 作者：Elias J. Sayour (1) (2)
  Pat McLendon (3)
  Roger McLendon (2)
  Gabriel De Leon (1) (4)
  Renee Reynolds (3)
  Jesse Kresak (5)
  John H. Sampson (2) (3)
  Duane A. Mitchell (1)
  
  1. University of Florida Brain Tumor Immunotherapy Program ; Preston A. Wells ; Jr. Center for Brain Tumor Therapy ; McKnight Brain Institute ; Department of Neurosurgery ; University of Florida ; 1149 South Newell Drive ; P.O. Box 100265 ; Gainesville ; FL ; 32610 ; USA
  2. Department of Pathology ; Duke University Medical Center ; Durham ; NC ; 27710 ; USA
  3. Duke Brain Tumor Immunotherapy Program ; Division of Neurosurgery ; Department of Surgery ; Duke University Medical Center ; Durham ; NC ; 27710 ; USA
  4. Department of Molecular Cancer Biology ; Duke University Medical Center ; Durham ; NC ; 27710 ; USA
  5. Department of Pathology ; University of Florida ; Gainesville ; FL ; 32608 ; USA
  
• 关键词：Tumor infiltrating lymphocytes ; Regulatory T cells (Tregs) ; Primary and recurrent GBM ; Immunotherapy
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：64
• 期：4
• 页码：419-427
• 全文大小：1,273 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

Glioblastoma multiforme (GBM) is an aggressive malignancy associated with profound host immunosuppression mediated in part by FoxP3 expressing regulatory CD4+ T lymphocytes (Tregs) that down-regulate anti-tumor immunity. In order to assess whether FoxP3 was an independent driver differentially expressed in primary versus recurrent GBMs, we stained resected primary and recurrent GBM tumors for CD3, CD4, CD8 and FoxP3 expression using standard immunohistochemistry. Slides were scanned with a high-resolution scanner (ScanScope CS; Aperio), and image analysis software (Aperio ScanScope) was used to enumerate lymphocyte subpopulations allowing for high-throughput analysis and bypassing manual selection bias. As shown in previous studies, enumeration of individual lymphocyte populations did not correlate with clinical outcomes in patients with GBM. However, the CD4+ to regulatory FoxP3+ T cell ratio was diminished in recurrent disease, and increased CD3 and CD8+ to regulatory T cell ratios showed a positive correlation with survival outcomes in primary GBM. These results suggest that while absolute numbers of tumor infiltrating lymphocytes may not be informative for predicting clinical outcomes in patients with GBM, the effective balance of CD3, CD4 and CD8+ T cells to immunosuppressive FoxP3+ regulatory cells may influence clinical outcomes in this patient population.