Circulating T-regulatory cells in PNET: A prospective study

Abstract

Bone marrow regulatory T-cells (Tregs) have been evaluated in patients with peripheral neuroectodermal tumor (PNET); data on peripheral blood circulating Tregs are lacking. The objective of our study was to determine baseline Tregs (both Treg frequency and absolute number) in patients with PNET and correlate with patient characteristics, and observe their change with treatment and relapse. Five milliliters blood was evaluated in de novo patients with PNET at diagnosis, post-neoadjuvant chemotherapy and at relapse/progression, along with nine healthy controls using flow-cytometric analysis for Treg cells (CD4+ CD25+ FoxP3+). Thirty-seven patients with median age 17 years; male/female ratio 5.1:1 had significantly higher baseline absolute Tregs than controls (mean 338.95 ± 264.63/mm(3) vs. 34.83 ± 24.90/mm(3); P < 0.001). Patients with fever had a significantly higher mean Treg frequency than those without fever (11.27 ± 8.36% vs. 8.40 ± 2.58%; P = 0.014). There was significant reduction in the circulating Tregs after neoadjuvant chemotherapy (mean 339.78 ± 294.31/mm(3) vs. 82.09 ± 91.25/mm(3), P < 0.001) and rise at progression (n = 13) as compared to values post-neoadjuvant chemotherapy (mean 240.92 ± 191.90/mm(3) vs. 57.67 ± 39.01/mm(3), P = 0.012). There was no significant difference in the event-free survival (EFS) or overall survival (OS) between the high and low Treg cell groups (2-year EFS 51.6% vs. 52.1%; P = 0.689 and OS 61.3% vs. 59.2%; P = 0.891). This study on circulating Tregs in PNET demonstrated that peripheral blood Tregs are higher in patients than healthy controls. There was significant reduction in Tregs with chemotherapy and rise at progression.