Prognositc Inpact of Tumor-Infiltrating FOXP3 + Regulatory T Cells in DLBCL Treated with R-CHOP

Tumor-infiltrating immune cells perform important functions in host immune reaction against tumor cells including diffuse large B cell lymphoma (DLBCL). Recently, variable tumor-infiltrating cells were reported to give a influence for prognosis, for example, regulatory T cell (T reg), cytotoxic T cell, macrophage and mast cell etc. Among these microenvironmental cells, we focused on Treg cell, and we assessed the distribution and prognostic significance of these cells in DLBCL. The forkhead/winged helix transcription factor 3 (FOXP3) is a transcriptional factorshown to be the key control gene in the development and function of Tregs both in mice and humans.

We examined samples from 94 patients (54 men and 40 women; median age, 70 years) at diagnosis who were prospectively enrolled between 2002 and 2008. All patients treated with R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). The pattern of FOXP3 protein expression was evaluated using immunehistochemistry in paraffin-embeded tissue samples. In addition, these samples were stained with antibodies for CD10, bcl-6 and MUM-1 via tissue microarray to classify into subgroups.

The median percentage of FOXP3+ cells was 91/mm2 (range 4–2100 /mm2). Patients with poor performance status (PS), and high serum lactate dehydrogenase (LDH) showed lower numbers of FOXP3+ cells. (PS; p= 0.014, LDH; p=0.0048) Patients with high counts of FOXP3+ cells (>90/mm2) have better prognosis than those of low counts (5 year (5-y) overall survival (OS); 72.1%, 49.7% p=0.024, respectively). Although no prognostic difference was observed between GCB type and non-GCB type (5-y OS: GCB 71.2%, non GCB 53.1%, p=0.12), low counts of FOXP3+ cell and non-GCB type patient was poorer prognosis than high counts and non GCB type. (low 5-y OS 31.2%, high 5-y OS 69.8% p=0.02).

Increased count of FOXP3+ tumor-infiltrating cell might predict better prognosis of DLBCL.

No relevant conflicts of interest to declare.