Work

Mb-94immunologic Profile of Patients With Newly-diagnosed Medulloblastoma at Initial Diagnosis and During Standard Radiation and Chemotherapy (pbtc-n11)

Year: 2016

Type: article

Abstract: BACKGROUND: The immunologic status of pts with MBL has not been well-characterized. OBJECTIVES: Evaluate circulating levels of immunosuppressive regulatory T cells (Tregs) in MBL compared to a control cohort of pts undergo craniectomy for Chiari malformation (CM) and determine the impact of standard radiation and chemotherapy on circulating levels of Tregs and other lymphocyte subsets. METHODS: A biological study of peripheral blood lymphocytes was undertaken within the Pediatric Brain Tumor Consortium (PBTC-N11). Eligibility criteria included age 4 - 21 yrs, pts 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 undergoing surgical resection and receiving dexamethasone as an anti-edema measure. Pts with confirmed MBL were also followed for longitudinal blood collection and analysis during radiotherapy and chemotherapy. RESULTS AND CONCLUSIONS: A total of 54 subjects were enrolled on the study (22- CM, 18- MBL, 14- non-MBL). Absolute number (P = 0.0002) and percentage (P = 0.0015) Tregs (CD4 + CD25 + FoxP3 + CD127low) at baseline were decreased in MBL compared to CM. Pts with MBL and non-MBL had significantly reduced overall CD4+ T cell count (P = 0.0005) compared to those with CM. Radiation and chemotherapy treatment reduced overall lymphocyte counts, however, within the CD4+ T cell compartment, Treg counts increased during treatment but gradually declined post therapy. These results demonstrate that pts with MBL exhibit overall reduced CD4+ T cell counts at diagnosis but not an elevated proportion of Tregs. Standard treatment exacerbates lymphopenia while enriching for immunosuppressive Tregs over time.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/now076.90