Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Background The tumor microenvironment is important for the behavior of cancer. We assessed the distribution and biological significance of FOXP3+ regulatory T-cells (Treg) in lymphomas. Design and Methods The absolute number of intratumoral FOXP3+ cells was immunohistochemically studied on lymphoma tissue microarrays from 1019 cases of different types of lymphomas and correlated to phenotypic and clinical parameters in uni- and multivariate models. Receiver operating characteristic -curves were used to determine prognostic cut-off values of FOXP3+ cell density. Results Of the 1019 cases, 926 (91%) were evaluable. FOXP3+ cell density varied between the lymphoma entities, and was highest in follicular lymphoma. An increased number of tumor-infiltrating FOXP3+ cells over the receiver operating characteristic-determined cut-offs positively influenced both disease-specific and failure-free survival in follicular lymphoma (p=0.053) and disease-specific survival in germinal center-like diffuse large B-cell lymphoma (p=0.051) and overall and failure-free survival in classical Hodgkin’s lymphoma (p=0.004), but had a negative prognostic effect in non-germinal center diffuse large B-cell lymphoma (p=0.059). In a Cox regression model, considering stage and age, the amount of FOXP3+ cells was of independent prognostic significance for failure-free survival in classical Hodgkin’s lymphoma and of borderline significance for overall survival in classical Hodgkin’s lymphoma and disease-specific survival in germinal center-like and non-germinal center diffuse large B-cell lymphoma. Conclusions FOXP3+ cells represent important lymphoma/host microenvironment modulators. Assessment of FOXP3+ cell density can contribute to the prediction of outcome in diffuse large B-cell lymphoma, fallicular lymphoma and classical Hodgkin’s lymphoma.