Differential cytokine expression in EBV positive peripheral T cell lymphomas

Abstract

Aim - To investigate whether specific cytokines are secreted locally at the tumour site in Epstein-Barr virus (EBV) positive peripheral T cell lymphoma (PTCL). Methods - An RNase protection assay system was used to study the differential expression of 21 cytokines in parallel in eight cases of EBV positive non-nasal PTCL, and compared with 11 EBV negative non-nasal PTCLs and three EBV positive nasal natural killer (NK) cell lymphomas. Results - Among the eight EBV positive cases, interferon γ (IFN-γ), lymphotoxin β (LTβ), interleukin 10 (IL-10), tumour necrosis factor a (TNF-α), transforming growth factor β1 (TGF-β1), and IL-1 receptor a (IL-Ra) were frequently detectable. IL-15, IL-6, IL-4, IL-1β, TNF-β, and IL-9 were sporadically detectable. Of the frequently detectable cytokines, IFN-γ and LTβ were commonly detected in the EBV negative cases. For cases with > 50% EBV encoded small non-polyadenylated RNA (EBER) positive cells, IL-10, TNF- α, and TGF-β1 were detected in three of three cases, and IL-1Ra in two of three cases. For cases with < 20% EBER positive cells, IL-10 was detected in three of five cases, TNF-α in two of four cases, but TGF-β1 and IL-1Ra were not detected. Interestingly, IL-6 was detected in two of three cases with > 50% EBER positive cells, but only in one of five cases with < 20% EBER positive cells. For comparison, in NK cell lymphomas, IL-10, TNF-α, IL-1Ra, and IL-6 were all detectable, but TGF-β was not detected at all. Immunohistochemical staining revealed IL-10 in many cells; in contrast, EBV latent membrane protein 1 (LMP1) was only found to be positive in isolated cells. Conclusions - Certain cytokines, such as IL-10 and TNF-α, might be expressed preferentially in EBV positive peripheral T cell lymphomas. It is likely that such a cytokine environment enhances EBV infection and contributes towards tumorigenesis.