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

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.