title: T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases.
abstract: BACKGROUND
  Tumour-infiltrating lymphocytes (TILs) have been shown to predict survival in numerous malignancies. The importance of TILs in primary pancreatic neuroendocrine tumours (NETs) and NET liver metastases (NETLMs) has not been defined.
  
  
  METHODS
  We identified 87 patients with NETs and 39 with NETLMs who had undergone resection. Immunohistochemistry was performed to determine TIL counts. Recurrence-free survival (RFS) and overall survival (OS) were determined using the log-rank test.
  
  
  RESULTS
  The median follow-up time was 62 months in NET patients and 48 months in NETLM patients. Vascular invasion and histologic grade were the only independent predictors of outcome for NETs and NETLMs, respectively. Analysis of intermediate-grade NETs indicated that a dense T cell (CD3+) infiltrate was associated with a median RFS of 128 months compared with 61 months for those with low levels of intratumoral T cells (P= 0.05, univariate analysis). Examination of NETLMs revealed that a low level of infiltrating regulatory T cells (Treg, FoxP3+) was a predictor of prolonged survival (P < 0.01, univariate analysis).
  
  
  CONCLUSIONS
  A robust T cell infiltrate is associated with improved RFS following resection of intermediate-grade NETs, whereas the presence of more Treg correlated with shorter OS after treatment of NETLMs. Further study of the immune response to intermediate-grade NETs and NETLMs is warranted.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Roger Williams Medical Center, Providence, RI, USA. skatz@rwmc.org
authors.forename: Steven C
authors.initials: SC
authors.lastname: Katz
authors.forename: Charan
authors.initials: C
authors.lastname: Donkor
authors.forename: Kristen
authors.initials: K
authors.lastname: Glasgow
authors.forename: Venu G
authors.initials: VG
authors.lastname: Pillarisetty
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.forename: N Joseph
authors.initials: NJ
authors.lastname: Espat
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: William
authors.initials: W
authors.lastname: Jarnagin
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Dematteo
authors.forename: Murray F
authors.initials: MF
authors.lastname: Brennan
authors.forename: Laura H
authors.initials: LH
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D019992:Databases as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; 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; D018358:Neuroendocrine Tumors / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D009519:New York City; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult