The Expression And Clinical Significance Of FOXP3-positive Tregs And IL-6 In Follicular Lymphoma Microenvironment

Purpose we employed the immunohistochemistry method to detect the expression of FOXP3- positive regulatory T cells( Tregs) and interleukin-6(IL-6) expression in follicular lymphoma( FL).Then we analyzed its relationship with patients'clinical Characteristics,response rate and survival.The main purpose for this clinical study is to explore the role of FOXP3~+Tregs and IL-6 in prediction of prognosis for and FL as well as to provide further information for therapeutic strategy making.Methods 43 cases of FL who underwent diagnosed between 2001 and 2010 at the Primary ffiliated Hospital of Anhui Medicial University and 10 lymphoid nodal and 10 reactive tonsils(control group). Immunohistochemistry method was applied to detect the FOXP3~+Tregs and IL-6 expression on the paraffin-embedded tissues of the selected cases.We analysed the relationship between FOXP3~+Tregs and IL-6 expression and patients'characteristics ,as well as its impacts on treatment response and survival were retrospectively analyzed with SPSS13.0 software pack. Results The relationship between the total number of FOXP3~+Tregs and patient's clinical characteristics such as ,performance status,Ann Arbor stage,serum LDH level,the number of extranodal sites,presence of B symptom and bone marrow involvement ,FLIPI,as well as its impacts on treatment response was investigated in non-parameter method but there was no significant correlation detected,however we found the P value less than 0.2 were age and histologic grade according to the tregs number,when the histologic grade and age were included in the analysis,only histologic grade showed significant difference between the histologic grade and the expression level of FOXP3~+Tregs by using a logistic regression (P<0.05)。As indicated by univariate analysis,the OS was significantly worse for patients with the following characteristics: histologic grade ,the expression level of FOXP3~+Tregs and IL-6 (P<0.05),but a multivarate analysis disclosed none of them was associated with patients'OS(P>0.05);There was statistically significant difference of FOXP3-positive Tregs in the follicular compartment and IL-6 was found between FL and normal tissue,and The number of FOXP3-positive Tregs negatively correlated with IL-6 (r_s =-0.608, P<0.05). Conclusions There was significant differences between the intrafollicular and interfollicular compartment inFL according to the total number of FOXP3~+Tregs (P<0.01); There was significant differences between the FL and reactive tonsils were found when analyzing the intrafollicular compartment according to the total number of FOXP3~+Tregs (P<0.05); There was statistically significant difference of IL-6 was found between FL and normal tissue (P<0.05); Less than 10% FOXP3-positive Tregs and grade 3 of IL-6 may be correlated with a poor outcome;As indicated by univariate analysis,the OS was significantly worse for patients with the following characteristics: histologic grade ,the expression level of FOXP3~+Tregs and IL-6 (P>0.05), but a Cox regression analysis indicated that histologic grade ,the expression level of FOXP3~+Tregs and IL-6 were not independent prognostic factors for FL (P>0.05); The number of FOXP3-positive Tregs negatively correlated with IL-6 suggestion that IL -6 may inhibit CD4 -positive Tcells differentiated into FOXP3~+Tregs .The clinical value of FOXP3~+Tregs and IL-6 in FL is worthy of further prospective clinical investigation.