title: Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients.
abstract: BACKGROUND
  Early stage lung cancer has a variable prognosis, and there are currently no markers that predict which patients will recur. This study examined the relation between tumor-regulatory T (Treg) cells and total tumor-infiltrating T-cell lymphocytes (TIL) to determine whether they correlated with recurrence.
  
  
  METHODS
  The authors reviewed all patients in our tissue databank from 1996 to 2001 and identified 64 consecutive pathologic stage I non-small cell lung cancer (NSCLC) patients who had surgical resection and at least a 2.5 years disease-free follow-up or documented recurrence within 2 years. Immunohistochemical analyses were performed on paraffin-embedded lung cancer tissue and the relation between Treg cells, TIL, and disease-specific survival was determined. A risk index was devised deductively for various possible combinations of Treg cells and TIL.
  
  
  RESULTS
  Treg cells and TIL were detected in 33 of 64 (51%) and 53 of 64 (83%) patients, respectively. When data were analyzed by using a Treg/TIL Combination Risk Index, patients with high-risk and intermediate-risk indices had hazard ratios of 8.2 (P = .007) and 3.3 (P = .109), respectively.
  
  
  CONCLUSIONS
  Patients with stage I NSCLC who have a higher proportion of tumor Treg cells relative to TIL had a significantly higher risk of recurrence. These data may be useful, particularly if combined with a panel of tumor markers, to suggest at the time of diagnosis which patients with seemingly early-stage NSCLC will relapse.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Petersen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Campa
authors.forename: Justin
authors.initials: J
authors.lastname: Sperlazza
authors.forename: Debbi
authors.initials: D
authors.lastname: Conlon
authors.forename: Mary-Beth
authors.initials: MB
authors.lastname: Joshi
authors.forename: David H
authors.initials: DH
authors.lastname: Harpole
authors.forename: Edward F
authors.initials: EF
authors.lastname: Patz
mesh_terms: D017252:CD3 Complex / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000276:immunology*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors