title: Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients.
abstract: The pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (T(regs)), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the T(reg) immunophenotypes in tumour-infiltrating lymphocytes (TILs), we performed a double-enzymatic immunostaining for detection of forkhead box P3 (FoxP3) and other markers including CD4, CD8, and CD25 on 64 NPC and 36 non-malignant nasopharyngeal (NP) paraffin-embedded tissues. Expression of CD3 zeta and CD3 epsilon was also determined. The prevalence of CD4(+)FoxP3(+) cells in CD4(+) T cells and the ratio of FoxP3(+)/CD8(+) were increased significantly in NPC compared with those in NP tissues (P < 0.001 and P = 0.025 respectively). Moreover, the ratio of FoxP3(+)/CD25(+)FoxP3(-) in NPC was significantly lower than that in NP tissues (P = 0.005), suggesting an imbalance favouring activated phenotype of T cells in NPC. A significant negative correlation between the abundance of FoxP3(+) and CD25(+)FoxP3(-) cells (P < 0.001) was also identified. When histological types of NPC were considered, a lower ratio of FoxP3(+)/CD25(+)FoxP3(-) was found in non-keratinizing and undifferentiated carcinomas. Increased CD4(+)FoxP3(+)/CD4(+) proportion and FoxP3(+)/CD8(+) ratio were associated with keratinizing squamous cell carcinoma. A reduced expression of CD3 zeta in TILs was found in 20.6% of the NPC tissues but none of the NP tissues. These data provide evidence for the imbalances of T(reg) and effector T cell phenotypes and down-regulation of signal-transducing molecules in TILs, supporting their role in suppression of immune response and immune evasion of NPC.
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: W K
authors.initials: WK
authors.lastname: Yip
authors.forename: M A
authors.initials: MA
authors.lastname: Abdullah
authors.forename: S M
authors.initials: SM
authors.lastname: Yusoff
authors.forename: H F
authors.initials: HF
authors.lastname: Seow
mesh_terms: D015415:Biomarkers / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002277:Carcinoma / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000276:immunology*; D009305:Nasopharynx / Q000276:immunology; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit