title: The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis.
abstract: BACKGROUND
  Tumour-infiltrating lymphocytes (TILs) are often found in tumours, presumably reflecting an immune response against the tumour. We carried out a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes based on the presence of TILs in cancer.
  
  
  METHODS
  A Pubmed and Embase literature search was designed. Studies were included, in which the prognostic significance of intratumoural CD3+, CD4+, CD8+, and FoxP3+ lymphocytes, as well as ratios between these subsets, were determined in solid tumours.
  
  
  RESULTS
  In pooled analysis, CD3+ TILs had a positive effect on survival with a hazard ratio (HR) of 0.58 (95% confidence interval (CI) 0.43-0.78) for death, as did CD8+ TILs with a HR of 0.71 (95% CI 0.62-0.82). FoxP3+ regulatory TILs were not linked to overall survival, with a HR of 1.19 (95% CI 0.84-1.67). The CD8/FoxP3 ratio produced a more impressive HR (risk of death: HR 0.48, 95% CI 0.34-0.68), but was used in relatively few studies. Sample size and follow-up time seemed to influence study outcomes.
  
  
  CONCLUSIONS
  Any future studies should be carefully designed, to prevent overestimating the effect of TILs on prognosis. In this context, ratios between TIL subsets may be more informative.
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: M J M
authors.initials: MJ
authors.lastname: Gooden
authors.forename: G H
authors.initials: GH
authors.lastname: de Bock
authors.forename: N
authors.initials: N
authors.lastname: Leffers
authors.forename: T
authors.initials: T
authors.lastname: Daemen
authors.forename: H W
authors.initials: HW
authors.lastname: Nijman
mesh_terms: D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology*; D011379:Prognosis