Assessment of peripheral blood T regulatory cells (Tregs) in PNET/Ewing sarcoma: A prospective study.

Abstract

9580 Background: Tregs in bone marrow have been previously evaluated in PNET patients; however, data on peripheral blood ccirculating Tregs is lacking. The objective of our study was to determine baseline Treg frequency in PNET patients and correlate the same with patient characteristics and outcome. Methods: Samples of 5ml venous blood were obtained from 38 newly diagnosed PNET patients at diagnosis along with six healthy controls. Flow cytometric analysis was done for detecting Treg cells [CD4+CD25+FoxP3+]. Results: Thirty-eight patients with median age 17 years; male/female ratio of 5.5:1 had significantly higher baseline Tregs than healthy controls [9.17%±.3.08 vs 3.16±1.49%; p=<0.0001]. Eight patients (21.1%) had fever at baseline presentation. The disease was extra-skeletal in one and metastatic at baseline in 11 (28.9%) patients. Ten patients relapsed on standard protocol of therapy and seven died. The median Treg frequency was 8.84% (Range: 2.49-16.31). When the Tregs were categorized as high and low based on the median value, patients with fever had a significantly higher Tregs than those without fever [11.3%±.3.5% vs 8.6% ±. 2.7%; p=0.02]. No significant association of peripheral blood Treg cells frequency was noted with other factors like age, sex, metastatic disease, relapse or death. The EFS was 55% and OS 70% of the entire cohort at a median follow up of 14 months. There was no significant difference in the EFS or OS between the high and low Treg cell groups [EFS- 52% vs 64%; p=0.99 and OS-75% vs 70%; p=0.26]. Conclusions: This is the first study on circulating Tregs in PNET, and it shows that the peripheral blood Treg frequencies are higher in these patients as compared to healthy controls. Further, PNET patients with fever had significantly higher Treg frequency. However, Tregs did not differ with respect to metastatic disease at presentation, EFS or OS.