Originally published as JCO Early Release 10.1200/JCO.2008.18.0513 on February 17 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Carreras, J. Articles by Campo, E. Search for Related Content PubMed PubMed Citation Articles by Carreras, J. Articles by Campo, E. Social Bookmarking                            What's this?

High Numbers of Tumor-Infiltrating Programmed Cell Death 1–Positive Regulatory Lymphocytes Are Associated With Improved Overall Survival in Follicular Lymphoma

From the Hematopathology Section, Departments of Pathology and Hematology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona, Barcelona; Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge; and Histopathology/In Situ Hybridization Facility, Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.

Corresponding author: Armando López-Guillermo, MD, Department of Hematology, Hospital Clinic, IDIBAPS, Villarroel 170, 08036-Barcelona, Spain; e-mail: alopezg{at}clinic.ub.es.

Purpose Tumor microenvironment influences the behavior of follicular lymphoma (FL), although the specific cell subsets involved are not well known. The aim of this study was to determine the impact of programmed cell death 1 (PD-1) –positive inhibitory immunoregulatory lymphoid cells in the clinicobiologic features and outcome of patients with FL.

Patients and Methods We examined samples from 100 patients (53 men and 47 women; median age, 54 years) at diagnosis, as well as in 32 patients at first relapse, with a recently generated monoclonal antibody against PD-1. The cells were quantified using computerized image analysis. Additional analysis consisted of double immunofluorescence and flow cytometry.

Results PD-1 expression was alternative to FOXP3 in lymphoid cells from both reactive tonsils and FL. At diagnosis, the median percentage of PD-1–positive cells was 14% (range, 0.1% to 74%). Patients with grade 3 FL, poor performance status, and high serum lactate dehydrogenase showed lower numbers of PD-1–positive cells. After a median follow-up of 6.2 years, patients with PD-1–positive cells 5% (n = 25), 6% to 33% (n = 50), and more than 33% (n = 25) had a 5-year progression-free survival rate of 20%, 46%, and 48% (P = .038) and overall survival (OS) of 50%, 77%, and 95% (P = .004), respectively. PD-1 and FL International Prognostic Index maintained prognostic value for OS in multivariate analysis. Patients with PD-1–positive cells 5% showed a higher risk of histologic transformation. At that time, transformed diffuse large B-cell lymphomas had lower percentage of PD-1–positive cells than FL.

Conclusion A high content of PD-1–positive cells predicted favorable outcome of FL patients, whereas a marked reduction is observed in transformation.

Supported by the Spanish Ministry of Education and Science (Grant No. SAF 05/5855), Spanish Ministry of Health (Grant No. PI070409), and Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Cáncer (Grant No. 2006-RET2039-O).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?