title: The prognostic value of Foxp3+ tumor-infiltrating lymphocytes in patients with glioblastoma.
abstract: Forkhead box protein 3 (Foxp3) is known as a specific marker for regulatory T cells which contribute to immunosuppression in tumor microenvironment. However, existing studies regarding clinical significance of Foxp3+ tumor-infiltrating lymphocytes (TILs) in glioblastoma (GBM) remained discrepant. In this study, we aimed to explore whether this subtype of TILs correlated with prognosis in patients with GBM. Foxp3+ TILs as well as CD8+ ones were detected by immunohistochemistry on paraffin-embedded tumor samples from 62 patients. Staining for p53, MGMT and Ki-67 were also performed. The correlation of TIL subtypes with clinicopathologic features were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared using log-rank test. Independent prognostic factors for PFS and OS were determined through univariate and multivariate analysis. Significant correlation was found between Foxp3 and CD8 expression (P = 0.003), but not between TIL subtypes and clinicopathologic characteristics. Patients with higher density of Foxp3+ TILs showed relatively shorter PFS (P < 0.001) and OS (P = 0.003) whereas patients with higher density of CD8+ TILs obtained no significant differences in survival. Survival analysis based on molecular classifications further clarified these predictive values. Univariate and multivariate analysis revealed that frequency of Foxp3+ TILs was probably associated with both PFS (P = 0.002) and OS (P = 0.003). In conclusion, the results suggest that Foxp3 positive infiltrates could provide an independent predictive factor in GBM.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, No. 12 Mid Wulumuqi Road, Shanghai, 200040, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yue
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Ye
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Zun-Guo
authors.initials: ZG
authors.lastname: Du
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000532:radiotherapy; D016827:CD8 Antigens / Q000378:metabolism; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005909:Glioblastoma / Q000175:diagnosis* / Q000532:radiotherapy; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes