The Density of Regulatory FOXP3+ T-Cells Is Associated with Caspase-3 Activation in Hodgkin/Reed-Sternberg Cells of Classical Hodgkin Lymphoma
E Drakos, GZ Rassidakis, EJ Schlette, TP Vassilakopoulos, C Kittas, AH Sarris, LJ Medeiros. The University of Texas M.D. Anderson Cancer Center, Houston, TX; National and Kapodistrian University of Athens, Athens, Greece; Hygeia Hospital, Athens, Greece
Background: FOXP3+ regulatory T-cells (T-regs) are critical for suppressing destructive overactivation of the immune system. Thus, T-regs might provide immunologic privilege to neoplastic cells facilitating their survival. By contrast, recent reports suggest that high numbers of FOXP3+ T-regs, which are prominent among the reactive population in classical Hodgkin lymphoma (cHL) are associated with favorable prognosis. However, the relationship between FOXP3+ T-regs and intrinsic biologic parameters of neoplastic Reed-Sternberg/Hodgkin (HRS) cells remains unknown.
Design: Expression of FOXP3, granzyme B and activated caspase-3 (aC3) were assessed by immunohistochemistry using specific monoclonal antibodies in 85 cHL tumors of previously untreated patients with available clinical data. FOXP3+ T-regulatory T-cells, granzyme B+ cytotoxic T-cells and aC3+ HRS cells were counted manually and FOXP3+ T-regs /HRS (FOXP3/HRS) and Granzyme B+ T-cells/HRS (GB/HRS) ratios were calculated.
Results: FOXP3+ T-regs, or cytotoxic Granzyme B+ T-cells were present in all cHL tumors. The FOXP3/HRS ratio in the study group ranged from 0,5 to 10,1 (mean 3.7, median 3.4, SD 2.1). The GB/HRS ratio ranged from 0,1 to 8 (mean 1, median 0.6, SD 1.4). The percentage of aC3+ HRS cells reflecting the rate of spontaneous apoptosis ranged from 0% to 4,3% (mean 1.3, median 0.8, SD 1.2). FOXP3/HRS or GB/HRS ratios were not correlated with clinical parameters including, gender, age, or stage of disease, or the presence of Epstein-Barr virus in HRS cells. Importantly, FOXP3/HRS ratio and percentage of aC3+ HRS cells were positively correlated (Spearman R=+0.58, p<0.001). However, FOXP3/HRS and GB/HRS ratios were not associated with failure-free or overall survival in this cHL study group.
Conclusions: High numbers of FOXP3+ T-regs seems to influence negatively the survival of HRS cells in cHL. The underlying mechanisms and potential therapeutic implications of this association merit further investigation.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 194, Wednesday Morning