Submitted April 20, 2006
Accepted June 20, 2006
High numbers of tumor infiltrating FOXP3-positive
regulatory T-cells are associated with improved overall
survival in follicular lymphoma
Joaquim Carreras, Armando Lopez-Guillermo, Bridget C Fox, Lluis Colomo, Antonio Martinez, Giovanna Roncador, Emili Montserrat, Elias Campo*, and Alison H Banham
Hospital Clinic, Barcelona, Spain
Nuffield Department of Clinical Laboratory Sciences, University of Oxford,John Radcliffe Hospital,UK
Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain
Hospital Clinic, University of Barcelona, Barcelona, Spain
* Corresponding author; email: ecampo{at}clinic.ub.es.
The tumor microenvironment plays an important role in
the biological behavior of follicular lymphoma (FL) but
the specific cell subsets involved in this regulation
are unknown. To determine the impact of FOXP3-positive
regulatory T cells (Treg) in the progression and outcome
of FL patients we examined samples from 97 patients at
diagnosis and 37 at first relapse with an anti-FOXP3
monoclonal antibody. Tregs were quantified using
computerized image analysis. The median overall survival
(OS) of the series was 9.9 years and the FL
International Prognostic Index (FLIPI) was
prognostically significant. The median Treg percentage
at diagnosis was 10.5%. Overall, 49 patients had more
than 10% Tregs, 30 between 5-10% and 19 less than 5%,
with a 5-year OS of 80%, 74% and 50%, respectively
(p=0.001). Patients with very low numbers of Tregs (<5%)
presented more frequently with refractory disease
(p=0.007). The prognostic significance of Treg numbers
was independent of the FLIPI. Seven transformed diffuse
large-B-cell lymphomas (DLBCL) had lower Treg
percentages (mean 3.3%) than FL grade 1,2 (mean 12.1%)
or 3 (mean 9%) (p<0.02). In conclusion, high Treg
numbers predict improved survival of FL patients, while
a marked reduction in Tregs is observed on
transformation to DLBCL.
