Classical Hodgkin Lymphoma with Positive Epstein-Barr Virus Status is Associated with More FOXP3 Regulatory T Cells
Antonia Pavlovic, Merica Glavina Durdov, Vesna Capkun, Jasminka Jakelic Pitesa, Maja Bozic Sakic
Department of Pathology, Forensic Medicine and Cytology, Clinical Hospital Center, Split, Croatia
Med Sci Monit 2016; 22:2340-2346
Available online: 2016-07-05
Classical Hodgkin lymphoma (cHL) is characterized by sparse malignant Hodgkin and Reed-Sternberg cells dispersed in an inflammatory microenvironment. Immune evasion of malignant cells is partially due to the existence of a subpopulation of immunosuppressive regulatory T cells (Treg). The aim of this study was to analyze T cell composition in cHL with special emphasis on Treg in regard to Epstein-Barr virus (EBV) status, subtype, and patient age.
MATERIAL AND METHODS: The study included 102 patients with cHL diagnosed during a 12-year period. EBV status of cHL was assessed immunohistochemically using antibodies directed to the EBV- encoded LMP1. To define T lymphocyte populations, slides were double-stained with FOXP3 for Treg, and CD4 or CD8 for T cells. In each case the number of single- and/or double-positive cells was counted on an image analyzer in 10 high-power fields. Statistical analysis was performed and differences were considered significant at P<0.05.
RESULTS: EBV-positive status of cHL was confirmed in 30 (29%) cases, mainly in patients older than 54 years and in mixed cellularity subtype. In EBV-positive cHL, higher numbers of CD8+ cells were found. In cHL with positive EBV status, more FOXP3+ Treg were found, as well as higher numbers of FOXP3+CD4+ Treg compared with EBV-negative cHL. The number of CD4+ cells decreased with age. The frequency of FOXP3+CD8+ Treg was variable, without a statistically significant association with age or EBV status.
CONCLUSIONS: EBV status has an impact on composition of T cell populations in the cHL microenvironment.
Keywords: Adult, Adolescent, Aged, 80 and over, CD8-Positive T-Lymphocytes - immunology, Child, Child, Preschool, Disease-Free Survival, Epstein-Barr Virus Infections - virology, Forkhead Transcription Factors - immunology, Herpesvirus 4, Human - isolation & purification, Hodgkin Disease - virology, T-Lymphocytes, Regulatory - immunology, Tumor Microenvironment - immunology