title: Tumour-infiltrating CD4(+) and CD8(+) lymphocytes as predictors of clinical outcome in glioma.
abstract: BACKGROUND
  T lymphocyte infiltration has been detected in glioma, although its significance remains unclear. The purpose of the present study was to explore the prognostic value of CD4(+) and CD8(+) tumour-infiltrating lymphocytes (TILs) in glioma, and the prognostic value of infiltrating Forkhead box protein 3 (FoxP3(+)) regulatory T cells were also investigated.
  
  
  METHODS
  CD4(+), FoxP3(+) and CD8(+) TILs were assessed by immunohistochemical staining of tissue microarray cores from 284 gliomas. Kaplan-Meier analysis and Cox proportional hazards models were used to examine the survival function of these TILs in 90 glioblastoma patients.
  
  
  RESULTS
  The number of CD8(+) TILs was inversely correlated with tumour grade (P=0.025), whereas the number of CD4(+) TILs was positively correlated with tumour grade (P=0.002). FoxP3(+) TILs were only observed in glioblastomas, but not in low-grade astrocytomas or oligodendroglial tumours. Among patients with glioblastoma, none of CD4(+) TILs, FoxP3(+) TILs and CD8(+) TILs alone was significantly associated with patient prognosis. However, the presence of high CD4(+) and low CD8(+) TIL levels was an independent predictor of poor progress-free survival (multivariate hazard ratio (HR) 1.618, 95% confidence interval (CI) 1.245-2.101, P<0.001) and poor overall survival (multivariate HR 1.508, 95% CI 1.162-1.956, P=0.002). Moreover, pseudoprogression was more often found in patients with high CD4(+) TILs and high CD8(+) TILs.
  
  
  CONCLUSIONS
  The combination of CD4(+) and CD8(+) TILs is a predictor of clinical outcome in glioblastoma patients, and a high level of CD4(+) TILs combined with low CD8(+) TILs was associated with unfavourable prognosis.
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing street 155, Heping district, Shenyang 110001, China.
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathology, China Medical University, Shenyang 110001, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing street 155, Heping district, Shenyang 110001, China.
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing street 155, Heping district, Shenyang 110001, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing street 155, Heping district, Shenyang 110001, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: T
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing street 155, Heping district, Shenyang 110001, China.
authors.forename: A
authors.initials: A
authors.lastname: Wu
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D019175:DNA Methylation; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D005910:Glioma / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D019139:Tumor Escape
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors