title: Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma.
abstract: BACKGROUND
  The tumor microenvironment is important for the behavior of cancer. We assessed the distribution and biological significance of FOXP3(+) regulatory T-cells (Treg) in lymphomas.
  
  
  METHODS
  The absolute number of intratumoral FOXP3(+) cells was immunohistochemically studied on lymphoma tissue microarrays from 1019 cases of different types of lymphomas and correlated to phenotypic and clinical parameters in uni- and multivariate models. Receiver operating characteristic -curves were used to determine prognostic cut-off values of FOXP3(+) cell density.
  
  
  RESULTS
  Of the 1019 cases, 926 (91%) were evaluable. FOXP3(+) cell density varied between the lymphoma entities, and was highest in follicular lymphoma. An increased number of tumor-infiltrating FOXP3(+) cells over the receiver operating characteristic-determined cut-offs positively influenced both disease-specific and failure-free survival in follicular lymphoma (p=0.053) and disease-specific survival in germinal center-like diffuse large B-cell lymphoma (p=0.051) and overall and failure-free survival in classical Hodgkin's lymphoma (p=0.004), but had a negative prognostic effect in non-germinal center diffuse large B-cell lymphoma (p=0.059). In a Cox regression model, considering stage and age, the amount of FOXP3(+) cells was of independent prognostic significance for failure-free survival in classical Hodgkin's lymphoma and of borderline significance for overall survival in classical Hodgkin's lymphoma and disease-specific survival in germinal center-like and non-germinal center diffuse large B-cell lymphoma.
  
  
  CONCLUSIONS
  FOXP3(+) cells represent important lymphoma/host microenvironment modulators. Assessment of FOXP3(+) cell density can contribute to the prediction of outcome in diffuse large B-cell lymphoma, fallicular lymphoma and classical Hodgkin's lymphoma.
authors.affiliation: Department of Pathology, University Hospital Basel, Schoenbeinstr. 40, CH-4031 Basel, Switzerland. atzankov@uhbs.ch
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.forename: Cecile
authors.initials: C
authors.lastname: Meier
authors.forename: Petra
authors.initials: P
authors.lastname: Hirschmann
authors.forename: Philip
authors.initials: P
authors.lastname: Went
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002452:Cell Count; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006689:Hodgkin Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors