Prognositc Inpact of Tumor-Infiltrating Cells Especially CD163 Positive Macrophage 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, cytotoxic T and macrophage cell, and we assessed the distribution and prognostic significance of these cells in DLBCL. Patients and Methods: We examined samples from 124 patients with DLBCL (69 men and 55 women; median age, 70 years) at diagnosis who were prospectively enrolled between 2002 and 2008. All patients were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). FOXP3 protein expression as Treg cells, CD8 expression as cytotoxic T cells, and CD163 expression as activated macrophage cells were evaluated by using immunohistochemistry in paraffin-embeded tissue samples. Results: The median count of FOXP3+ cells was 15.2/mm² (×400) (range 1– 350/mm²), the median of CD8+ cells was 72/mm² (8−402) and the median of CD163+ cells was 24/mm² (0−114). Patients with high count of FOXP3+ cells (>15/mm²) have better prognosis than those of low count (5 year (5-y) overall survival (OS); 72.1%, 49.7% p=0.024, respectively). No significant difference was observed for progression free survival (PFS) of FoxP3 expression. No significant difference was observed for OS and PFS of CD8 expression. Patients with low count of CD163+ cells (<15/mm²) have better prognoses than those of high count (5-y OS; 80.1%, 52.5% p=0.009, 5-y PFS: 84.3%, 42.9% p=0.0019, respectively). Multivariate analyses employing factors such as poor risk group of revised International Prognostic Index (R-IPI), non-GCB type of subtype and low counts of FoxP3, low count of CD8, and high count of CD163 demonstrated that CD163 and R-IPI for OS and PFS were independent prognostic factors (OS; CD163 odd's ratio: 2.56, p=0.038, R-IPI: 2.66, p=0.015, PFS; CD163: 2.73, p=0.03, R-IPI: 2.56, p= 0.012). Conclusion: The count of tumor-infiltrating cells especially CD163+ macrophage might predict prognosis of DLBCL treated with R-CHOP.

No relevant conflicts of interest to declare.