The composition of the microenvironment in follicular lymphoma is associated with the stage of the disease.

The role of regulatory and follicular helper T-cells as prognostic markers in follicular lymphoma was evaluated within the setting of prospective, randomized trials because the previously published results were contradictory. Two hundred sixty-four diagnostic tissue specimens from patients suffering from follicular lymphoma who received therapy within prospective randomized trials of the German Low Grade Lymphoma Study Group were analyzed immunohistochemically for FoxP3 and PD-1 expression to detect regulatory and follicular helper T-cells, respectively. We did not find any correlation between the content of regulatory and follicular helper T-cells and the time to treatment failure or overall survival in patients with advanced stages of follicular lymphoma in need of treatment. However, a perifollicular pattern of regulatory T-cells was associated with a poorer prognosis. The content of regulatory T-cells was positively and the content of follicular helper T-cells inversely correlated with a higher stage of the disease at diagnosis, implying that the microenvironment changes during tumor dissemination. This finding is independent of any therapy administered and needs to be considered when possible biomarkers related to the microenvironment of follicular lymphoma are studied.