title: Increased levels of tumor-infiltrating lymphocytes are associated with improved recurrence-free survival in stage 1A non-small-cell lung cancer.
abstract: BACKGROUND
  Tumor-infiltrating lymphocytes (TILs) have been found to increase survival in many forms of cancer, including, endometrial, bile ductal, colonic, esophageal, and urothelial cancers, as well as melanoma and follicular lymphoma. The relevance of TILs in the prognosis of non-small-cell lung cancer (NSCLC), however, still remains controversial. We compared the outcomes of stage 1A NSCLC with and without tumor infiltrating lymphocytes to evaluate the effects of TILs on recurrence and survival patterns.
  
  
  METHODS
  From 2000 to 2009, 273 anatomic segmentectomies and lobectomies were performed on stage 1A NSCLC. Patients were stratified into TIL- and TIL+ cohorts based on pathologic evaluation. Further investigation was conducted on the effects of TILs in patients with and without angiolymphatic invasion. Variables analyzed include overall survival, recurrence-free survival, and type of recurrence.
  
  
  RESULTS
  Overall 5-y survival was not affected by TIL status (65% versus 60%, P = 0.469). Five-year recurrence-free survival (RFS) was significantly increased in the TIL+ group versus the TIL- group (87% versus 73%, P = 0.011), most significantly in women (P = 0.016). The presence of angiolymphatic invasion (ALI) was associated with decreased 5-y RFS versus patients without ALI (61% versus 85%, P < 0.001). Interestingly, in the ALI negative group, TIL+ patients experienced a significantly increased 5-y recurrence-free survival versus TIL- patients (93% versus 80%, P = 0.036).
  
  
  CONCLUSIONS
  High levels of intratumoral TILs are associated with improved recurrence-free survival in stage 1A NSCLC patients as well as a reduced likelihood of systemic recurrence. When angiolymphatic invasion is not present, the beneficial effects of TILs become even more profound.
authors.affiliation: Division of Thoracic Surgery, Heart, Lung, and Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15232, USA. hornezd@gmail.com
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Horne
authors.forename: Robert
authors.initials: R
authors.lastname: Jack
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Gray
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: David O
authors.initials: DO
authors.lastname: Wilson
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Yousem
authors.forename: Katie S
authors.initials: KS
authors.lastname: Nason
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Landreneau
authors.forename: James D
authors.initials: JD
authors.lastname: Luketich
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schuchert
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009367:Neoplasm Staging / Q000401:mortality; D011013:Pneumonectomy / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate