Higher infiltration of intratumoral CD25+ FOXP3+ lymphocytes correlates with a favorable prognosis in patients with diffuse large B-cell lymphoma.

Regulatory T-cells (Tregs) play an important role in cancer immunity but their prognostic impact is controversial in diffuse large B-cell lymphoma (DLBCL). Intratumoral Tregs in DLBCL (n = 70) were evaluated by double-stained CD25 and FOXP3 lymphocytes in formalin-fixed paraffin-embedded tissues, and correlated with clinicopathologic features. We found that increased numbers of intratumoral FOXP3+ lymphocytes (>2.4/HPF) and CD25 + FOXP3+ lymphocytes (>0.8/HPF) are favorable prognosticators (p = .004 and p < .001, respectively) in DLBCL patients, along with age <70 years, stage I-II disease, normal serum LDH level and low IPI scores (p < .001, .002, .002, and <.001, respectively). On multivariate analyses, a higher number of CD25 + FOXP3+ lymphocytes retained prognostic significance (p = .040). Interestingly, higher Treg infiltration correlated with increased infiltration by cytotoxic T-lymphocytes (γ = 0.294, p = .038) and nodal location (γ = 0.390, p = .004), but not with infiltration by CD123+ plasmacytoid dendritic cells, which were reported to induce Tregs with immune tolerance. Therefore, congruent with literature meta-analyses, higher intratumoral CD25 + FOXP3+ lymphocytes have a beneficial impact on DLBCL.