Cancer Immunology, Immunotherapy

, Volume 66, Issue 12, pp 1589–1595 | Cite as

Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)

  • Sridharan Gururangan
  • Elizabeth Reap
  • Robert Schmittling
  • Mehmet Kocak
  • Renee Reynolds
  • Gerald Grant
  • Arzu Onar-Thomas
  • Patricia Baxter
  • Ian F. Pollack
  • Peter Phillips
  • James Boyett
  • Maryam Fouladi
  • Duane Mitchell
Original Article

Abstract

Background

We evaluated circulating levels of immunosuppressive regulatory T cells (Tregs) and other lymphocyte subsets in patients with newly diagnosed medulloblastoma (MBL) undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation (CM) and further determined the impact of standard irradiation and chemotherapy on this cell population.

Methods

Eligibility criteria for this biologic study included age 4–21 years, patients with CM undergoing craniectomy (as non-malignant surgical controls) and receiving dexamethasone for prevention of post-operative nausea, and those with newly diagnosed posterior fossa tumors (PFT) undergoing surgical resection and receiving dexamethasone as an anti-edema measure. Patients with confirmed MBL were also followed for longitudinal blood collection and analysis during radiotherapy and chemotherapy.

Results

A total of 54 subjects were enrolled on the study [22-CM, 18-MBL, and 14-PFT]. Absolute number and percentage Tregs (defined as CD4+CD25+FoxP3+CD127low/−) at baseline were decreased in MBL and PFT compared to CM [p = 0.0016 and 0.001, respectively). Patients with MBL and PFT had significantly reduced overall CD4+ T cell count (p = 0.0014 and 0.0054, respectively) compared to those with CM. Radiation and chemotherapy treatment in patients with MBL reduced overall lymphocyte counts; however, within the CD4+ T cell compartment, Tregs increased during treatment but gradually declined post therapy.

Conclusions

Our results demonstrate that patients with MBL and PFT exhibit overall reduced CD4+ T cell counts at diagnosis but not an elevated proportion of Tregs. Standard treatment exacerbates lymphopenia in those with MBL while enriching for immunosuppressive Tregs over time.

Keywords

Medulloblastoma Immunotherapy Regulatory T cells CD4 Posterior fossa tumors 

Abbreviations

CM

Chiari malformation

GBM

Glioblastoma multiforme

MBL

Medulloblastoma

PFT

Posterior fossa tumors other than medulloblastoma

RT

Radiotherapy

TH

Helper T cells

Tregs

Regulatory T cells

Supplementary material

262_2017_2051_MOESM1_ESM.pdf (22 kb)
Supplementary material 1 (PDF 21 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Sridharan Gururangan
    • 1
    • 2
  • Elizabeth Reap
    • 3
  • Robert Schmittling
    • 3
  • Mehmet Kocak
    • 10
    • 11
  • Renee Reynolds
    • 4
  • Gerald Grant
    • 5
  • Arzu Onar-Thomas
    • 10
  • Patricia Baxter
    • 6
  • Ian F. Pollack
    • 7
  • Peter Phillips
    • 8
  • James Boyett
    • 10
  • Maryam Fouladi
    • 9
    • 10
  • Duane Mitchell
    • 1
    • 2
  1. 1.The Preston A. Wells Center for Brain Tumor Therapy, McKnight Brain InstituteUniversity of FloridaGainesvilleUSA
  2. 2.Department of NeurosurgeryUniversity of FloridaGainesvilleUSA
  3. 3.Immunotherapy ProgramDuke University Medical CenterDurhamUSA
  4. 4.Department of NeurosurgeryState University of New YorkBuffaloUSA
  5. 5.Department of NeurosurgeryStanford UniversityStanfordUSA
  6. 6.Texas Children’s Cancer CenterHoustonUSA
  7. 7.Department of NeurosurgeryChildren’s Hospital of PittsburghPittsburghUSA
  8. 8.Neuro-Oncology ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  9. 9.Neuro-Oncology ProgramCincinnati Children’s HospitalCincinnatiUSA
  10. 10.Operations, Biostatistics, and Data Management CenterThe Pediatric Brain Tumor ConsortiumMemphisUSA
  11. 11.University of Tennessee Health Science CenterMemphisUSA

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