Expression of programmed death-1 (CD279) in primary cutaneous B-cell lymphomas with correlation to lymphoma entities and biological behaviour

Background Programmed death-1 (PD-1/CD279) is a cell-surface protein expressed in activated T cells and a subset of T lymphocytes including follicular helper T cells (TFH). The interaction between PD-1 and its ligands plays a role in immune response and evasion of malignancies. In nodal follicular lymphoma, the number of intratumoral PD-1-positive lymphocytes is associated with overall survival. Objectives To investigate 28 cases of primary cutaneous B-cell lymphoma, including the subtypes PCFCL (n=10), PCMZL (n=10) and DLBCL-LT (n=8) for the number and density of PD-1-positive cells. Methods Immunohistochemical staining and a computerized morphometric analysis for evaluation were applied. The results were correlated with the clinical outcome. To distinguish between activated T cells and TFH we performed PD-1/bcl-6 double staining and compared these results with CXCL-13 staining. Double staining for PD-1 and PAX-5 was used to investigate whether tumour cells were positive for PD-1. Results The PD-1-positive cells represented tumour-infiltrating T cells (TILs). Only a minor subset was represented by TFH. Patients with DLBCL-LT had a significantly lower number of PD-1-positive TILs than those with PCMZL (P=0012) and PCFCL (P=0002) or both (P=0001). The difference between PCMZL and PCFCL did not reach significance (P=0074). The tumour cells were negative for PD-1. Conclusions A higher number of PD-1-expressing cells was found in indolent PCMZL and PCFCL than in high-malignant DLBCL-LT. The PD-1-positive cells represented not only TFH, but also other activated T cells as a part of the tumour microenvironment. The tumour cells in all investigated types of PCBCL did not show aberrant PD-1 expression.