title: Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms.
abstract: BACKGROUND
  Tumor-infiltrating lymphocytes (TIL) are considered important in anticancer immunosurveillance, although their role has not been clearly established yet. We examined prevalence, correlations, and prognostic significance of TIL among our patient population of resected lung neoplasms.
  
  
  METHODS
  From 1993 to 2006, the presence of TIL was retrospectively evaluated in 1,290 patients operated on for primary lung neoplasms. Tumor-infiltrating lymphocytes were defined as those intraepithelial lymphocytes located within the cancer cell nests.
  
  
  RESULTS
  Tumor-infiltrating lymphocytes were detected in 294 patients (23%). A significant difference was found between prevalence in non-small cell lung carcinomas versus neuroendocrine tumors (290 of 1,208, 24% versus 4 of 82, 5%; p = 0.0001). Prevalence was similar in adenocarcinomas, squamous-cell carcinomas, and large-cell anaplastic carcinomas. Logistic regression analysis indicates that TIL correlate with grading (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55; p = 0.02), tumor dimension (odds ratio, 0.86; 95% confidence interval, 0.79 to 0.94; p = 0.0008), and vascular invasion (odds ratio, 1.62; 95% confidence interval, 1.21 to 2.16; p = 0.0009). A not significantly better survival in the presence of TIL was observed overall (p = 0.20), becoming significant in squamous-cell carcinomas (p = 0.03). In patients with stage I disease, TIL is associated with a significant survival advantage in squamous-cell carcinomas (p = 0.03). The survival advantage increases with the duration of follow-up and is more evident after 4 to 6 years.
  
  
  CONCLUSIONS
  Tumor-infiltrating lymphocytes are observed in about one fourth of resected lung neoplasms: they are rare in neuroendocrine tumors. Tumor-infiltrating lymphocytes are more frequent in poorly differentiated tumors and in tumors with microscopic vascular invasion. The presence of TIL correlates with an improved survival in squamous cell carcinomas, particularly at early stage. The survival advantage increases with the duration of follow-up.
authors.affiliation: Department of Thoracic Surgery, University of Torino, Torino, Italy. enrico.ruffini@unito.it
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
authors.forename: Sofia
authors.initials: S
authors.lastname: Asioli
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Filosso
authors.forename: Paraskevas
authors.initials: P
authors.lastname: Lyberis
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Bruna
authors.forename: Luigia
authors.initials: L
authors.lastname: Macrì
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Daniele
authors.forename: Alberto
authors.initials: A
authors.lastname: Oliaro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor