title: The correlation between tumor-infiltrating Foxp3+ regulatory T cells and cyclooxygenase-2 expression and their association with recurrence in resected head and neck cancers.
abstract: The aim of this study was to investigate the correlation between tumor-infiltrating CD4+ CD25(high) Foxp3+ naturally occurring regulatory T cells (Foxp3+ nTregs) and cyclooxygenase-2 (COX-2) expression and their association with local recurrence in resected head and neck cancers. Intratumoral COX-2 and Foxp3+ nTregs expressions were retrospectively assessed using immunohistochemistry. Associations between the clinicopathological characteristics and either intratumoral COX-2 expression or number of Foxp3+ nTregs were tested using the Chi-square test. The correlation between the number of Foxp3+ nTregs and COX-2 expression was tested using Spearman's rank correlation test. Associations between recurrence-free survival (RFS) and either intratumoral COX-2 expression or number of Foxp3+ nTregs were calculated using the Kaplan-Meier method, and factors that may influence the RFS were analyzed by Cox regression. The five-year RFS for all patients was 35.09%. Patient clinicopathological characteristics had no relationship with intratumoral COX-2 expression or the number of Foxp3+ nTregs. However, a positive correlation between intratumoral COX-2 expression and the number of Foxp3+ nTregs was observed (P < 0.001). The RFS of patients with elevated COX-2 expression was significantly worse than that of patients without intratumoral COX-2 expression (P = 0.0228). The RFS of patients with tumors containing >6 Foxp3+ cells was significantly worse than that of patients with tumors containing ≤6 Foxp3+ cells (P = 0.0020). However, by Cox regression analysis, the RFS of all patients was not influenced by intratumoral COX-2 expression (P = 0.100) or the number of Foxp3+ nTregs (P = 0.071). Tumor-infiltrating CD4+ CD25(high) Foxp3+ nTregs were positively correlated with intratumoral COX-2 expression and were associated with a worse RFS in univariate analysis.
authors.affiliation: Cancer center, The Second Hospital of Shandong University, No 247 Beiyuan Avenue, 250033 Jinan, Shandong Province, China.
authors.forename: Dian-Shui
authors.initials: DS
authors.lastname: Sun
authors.forename: Miao-Qing
authors.initials: MQ
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human