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01-12-2017 | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 12/2017

Abstract

Background

We evaluated circulating levels of immunosuppressive regulatory T cells (T_regs) 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 T_regs (defined as CD4⁺CD25⁺FoxP3⁺CD127^low/−) 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, T_regs 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 T_regs. Standard treatment exacerbates lymphopenia in those with MBL while enriching for immunosuppressive T_regs over time.

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Title: Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)
Authors: 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
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 12/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-017-2051-6

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