Increased Tumor Infiltrating FOXP3+ Regulatory T-Cells Are Associated with Improved Survival in Classical Hodgkin Lymphoma

Background: Regulatory T-cells (Tregs), a CD4+, CD25+, FOXP3+ subset, appear to modulate the tumor microenvironment in lymphoma. Using FOXP3 expression as a marker of Tregs, single series have suggested that higher numbers of tumor infiltrating FOXP3+ cells are associated with improved survival in both follicular lymphoma and classical Hodgkin lymphoma (cHL). However, neither of these findings has been confirmed by separate studies and, in fact, contradictory data exists. We sought to evaluate potential correlations between the number of FOXP3+ cells in the tumor microenvironment and patient outcome. Methods: 98 previously untreated cHL patients, biopsied and treated with curative intent at the Cleveland Clinic, were studied. FOXP3 was assessed by immunohistochemistry (Abcam) and quantitated as the number of positive cells per high power field (hpf), averaged over 5 fields. Histology was evaluated and medical records were reviewed for clinical features (including gender, age, stage, B symptoms, bulk, number of sites and IPS), lymphoma progression and death. Results: The mean number of FOXP3+ cells (±standard deviation) was 41.7 ± 33.9 cells/hpf, and the median number was 36.4 cells/hpf (range 0–152.0 cells/hpf). Higher numbers of FOXP3+ T-cells were associated with age25.0 FOXP3+ cells/hpf compared to 81% ± 6% for patients with Conclusion: FOXP3+ T cells are a favorable prognostic marker in cHL and reflect the importance of the immune response thus providing rationale for the use of immunomodulatory therapies in these patients. Failure Free Survival Failure Free Survival Overall Survival Overall Survival