title: Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases.
abstract: BACKGROUND
  Tumor-infiltrating lymphocyte (TIL) counts in colorectal cancer liver metastases (CRCLM) predict survival following resection. While CD4 and CD8 T cells have been correlated with outcome following CRCLM resection, the role of regulatory T cells (Treg) is not well defined.
  
  
  METHODS
  TIL in 188 patients who underwent CRCLM resection between 1998 and 2000 were analyzed by immunohistochemistry using tissue microarrays. Correlation between TIL composition and outcome was determined while controlling for established prognostic factors. Total T cells (CD3), helper T cells (CD4), cytotoxic T cells (CD8), and Treg (FoxP3) were analyzed.
  
  
  RESULTS
  Median follow-up time was 40 months for all patients and 95 months for survivors. Overall survival (OS) at 5 and 10 years was 40 and 25%, respectively. The CD4 T cell count correlated with OS (p = .02) and recurrence-free survival (p = .04). A high number of CD8 T cells relative to total T cells (CD8:CD3 ratio) predicted longer OS times (p = .05). Analysis of Treg revealed that high FoxP3:CD4 (p = .03) and FoxP3:CD8 (p = .05) ratios were independent predictors of shorter OS. Patients with a high clinical risk score (CRS) were more likely to have a high number of intratumoral Treg, and patients ≥65 years old had a less robust CRCLM T cell infiltration.
  
  
  CONCLUSIONS
  A high number of Treg relative to CD4 or CD8 T cells predicted poor outcome, suggesting an immunosuppressive role for FoxP3 + TIL. The intratumoral immune response was an independent predictor of outcome in patients with colorectal liver metastases.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. skatz@rwmc.org
authors.forename: Steven C
authors.initials: SC
authors.lastname: Katz
authors.forename: Zubin M
authors.initials: ZM
authors.lastname: Bamboat
authors.forename: Ajay V
authors.initials: AV
authors.lastname: Maker
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Venu G
authors.initials: VG
authors.lastname: Pillarisetty
authors.forename: Adam C
authors.initials: AC
authors.lastname: Yopp
authors.forename: Cyrus V
authors.initials: CV
authors.lastname: Hedvat
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors