Prognostic value of FOXP3 and TGF-beta expression in both peripheral blood and lymph nodes in patients with B-Non Hodgkin's lymphoma

ABSTRACT

Foxp3 has been studied as a biomarker of Treg cells in many solid malignant diseases, although its role as an immunomodulator in B-NHL remain poorly understood and the effect of traditional chemotherapy on its expression remains unclear. In this study the role of circulating and intra-tumoral Treg and TGF-beta in patients with B-NHL before and after chemotherapy was evaluated. Enumeration of Treg cells was carried out by flow cytometric staining of their cell surface markers CD4 and CD25 as well as by molecular analysis of its signature transcription factor FoxP3. Expression of FoxP3 was done using quantitative real-time PCR while TGF-beta mRNA expression was semi-quantitatively assayed by the conventional reverse transcription-PCR. In addition, spontaneous versus mitogen-induced release of TGF-beta by PBMCs was assessed by a short term cell culture followed by ELISA. This was done before and after six cycles of CHOP chemotherapy. The results were evaluated in relation to the clinicopathological data. A significant increase in mRNA transcripts of both Fox P3 and TGF-beta as well as the percentage of CD4[+] /CD25[+] in B-NHL patients before receiving the chemotherapy were recorded, when compared either to healthy controls or to patients after completion the treatment regimen. Interestingly 6 cycles of CHOP treatment caused significant reduction in all parameters under study