Increased quantity of tumor-infiltrating FOXP3-positive regulatory T cells is an independent predictor for improved clinical outcome in extranodal NK/T-cell lymphoma

Patients and methods: We collected 64 NKTCL cases and numerically quantified the amount of tumor-infiltrating FOXP3-positive Tregs by automated slide scanning and image analysis program after immunohistochemical staining using anti-FOXP3 antibody. Results: Patients were able to be classified into two end groups by their level of Tregs. Twenty-eight (44%) patients had Tregs < 50/0.40 mm(2), while 36 (56%) had Tregs >= 50/0.40 mm(2) within the tumor. The decreased number of Tregs (< 50/0.40 mm(2)) was more common in patients with poor performance status or in those presented in non-upper aerodigestive tract. However, the level of Tregs was not associated with other prognostic factors, including stage, lactate dehydrogenase level, International Prognostic Index, and NKTCL Prognostic Index. Importantly, patients with increased numbers of Tregs (>= 50/0.40 mm(2)) showed prolonged overall and progression-free survival (P = 0.0005 and P = 0.0079, respectively). The number of FOXP3-positive Tregs was an independent prognostic factor (P = 0.001) by multivariate analysis. Conclusion: Increased quantity of tumor-infiltrating Tregs predicted improved clinical outcome in NKTCL patients.