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


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 > or =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 (> or =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.


CONCLUSIONS
Increased quantity of tumor-infiltrating Tregs predicted improved clinical outcome in NKTCL patients.
Kim
W Y
WY
Department of Pathology, Seoul National University Hospital, Seoul, Korea.
Jeon
Y K
YK
Kim
T M
TM
Kim
J E
JE
Kim
Y A
YA
Lee
S-H
SH
Kim
D-W
DW
Heo
D S
DS
Kim
C-W
CW
D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D055611:Natural Killer T-Cells / Q000276:immunology*; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors