Soluble programmed cell death protein 1 (sPD-1) and the soluble programmed cell death ligands 1 and 2 (sPD-L1 and sPD-L2) in lymphoid malignancies.

Background The programmed cell death protein 1 (PD-1) and its ligand 1 and 2 (PD-L1/PD-L2) regulates the immune system and the checkpoint pathway can be exploited by malignant cells to evade anti-tumor immune response. Soluble forms (sPD-1/sPD-L1/sPD-L2) exist in the peripheral blood, but their biological and clinical significance is unclear. Method Time-Resolved Immunofluorometric Assay (TRIFMA) and Enzyme-Linked Immunosorbent Assay (ELISA) were used to measure sPD-1, sPD-L1 and sPD-L2 levels in serum from 131 lymphoma patients and 22 healthy individuals. Results Patients had higher sPD-1 and sPD-L2 levels than healthy individuals. In Diffuse Large B-cell Lymphoma, patients with high International Prognostic Index score had higher sPD-1 levels and sPD-L2 levels correlated with subtype according to cell of origin. Compared to other lymphoma types, follicular lymphoma displayed higher sPD-1 and lower sPD-L1 levels along with lower ligand/receptor ratios. Conclusion This is the first study to simultaneously characterize pre-therapeutic sPD-1, sPD-L1 and sPD-L2 in a variety of lymphoma subtypes. The relation between higher sPD-1 levels and adverse prognostic factors as suggests a possible biological role and potential clinical usefulness of sPD-1. Moreover, the reverse expression pattern in follicular lymphoma and T-cell lymphoma/leukemia may reflect biological information relevant for immunotherapy targeting the PD-1-pathway.