Annals of Oncology Advance Access originally published online on June 19, 2009
Annals of Oncology 2009 20(10):1688-1696; doi:10.1093/annonc/mdp056
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hematologic malignacies |
Increased quantity of tumor-infiltrating FOXP3-positive regulatory T cells is an independent predictor for improved clinical outcome in extranodal NK/T-cell lymphoma
1 Department of Pathology, Seoul National University Hospital
2 Tumor Immunity Medical Research Center, Cancer Research Center, Seoul National University College of Medicine
3 Department of Internal Medicine, Seoul National University College of Medicine
4 Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea
* Correspondence to: Prof. Y. K. Jeon, Department of Pathology, Seoul National University Hospital, 28 Yeongeon-dong, Jongro-gu, Seoul 110-799, Korea. Tel: +82-2-2072-1347; Fax: +82-2-743-5530; E-mail: junarplus{at}chol.com
Background: Extranodal natural killer/T-cell lymphoma (NKTCL) is a clinically heterogeneous disease with a poor prognosis, requiring risk-stratified management in affected patients. Recently, tumor microenvironment including regulatory T cells (Tregs) has been implicated as a prognostic marker in certain types of 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 mm2, while 36 (56%) had Tregs 
50/0.40 mm2 within the tumor. The decreased number of Tregs (<50/0.40 mm2) 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 mm2) 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.
Key words: EBV, extranodal NK/T-cell lymphoma, FOXP3, regulatory T cells
These authors contributed equally to this work as corresponding authors. Received for publication October 28, 2008. Revision received February 11, 2009. Accepted for publication February 12, 2009.