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

Published

Journal Article

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.

Full Text

Cited Authors

  • Gururangan, S; Reap, E; Schmittling, R; Kocak, M; Reynolds, R; Grant, G; Onar-Thomas, A; Baxter, P; Pollack, IF; Phillips, P; Boyett, J; Fouladi, M; Mitchell, D

Published Date

  • December 2017

Published In

Volume / Issue

  • 66 / 12

Start / End Page

  • 1589 - 1595

PubMed ID

  • 28825123

Pubmed Central ID

  • 28825123

Electronic International Standard Serial Number (EISSN)

  • 1432-0851

Digital Object Identifier (DOI)

  • 10.1007/s00262-017-2051-6

Language

  • eng

Conference Location

  • Germany