Expression of PD-1 (CD279) and FoxP3 in diffuse large B-cell lymphoma

The role of the microenvironment in high-grade lymphoma is not well defined. In this report, we employ immunohistochemistry to characterise programmed death-1 (PD-1/CD279) and FoxP3 expression in 70 cases of diffuse large B-cell lymphoma (DLBCL). PD-1 is a surface marker characteristic of follicular helper T-cells whilst FoxP3 is characteristic of Tregs. We demonstrate variable infiltration with CD4⁺ T-cells (<10 to >50 % of all lymph node cells) and PD-1^hi cells (0.1 to 1.5 % of all cells). CD4⁺ T-cells can be distributed in clusters or more diffusely and PD-1^hi cells, but not FoxP3⁺ cells, are found in rosettes around lymphoma cells. Cases with high CD4⁺ T-cell numbers tended to have higher numbers of both PD-1^hi and FoxP3⁺ cells. Cases with total CD4⁺ T-cell, PD-1^hi and FoxP3⁺ numbers above the median associate with better clinical outcome. Overall, we demonstrate that infiltration by CD4⁺ T-cells, including both FoxP3⁺ and PD-1^hi subsets, correlates with prognosis in DLBCL. In distinction to previous reported series, patients (91 %) were treated with rituximab-containing regimens, suggesting that the effects of CD4+ T-cell infiltration are maintained in the rituximab era. This work suggests that determinants of total CD4⁺ T-cell infiltration, either molecular characteristics of the lymphoma or the patients’ immune system, and not individual T-cell subsets, correlate with clinical outcome.