Soluble CD95L is a prognostic marker in central nervous system posttransplant lymphoproliferative disorders

CD95L is a transmembrane cytokine mainly expressed by activated T and natural killer cells to contract the immune response through cell-cell contact. Conversely, after cleavage by metalloproteases, this ligand releases a soluble CD95L (sCD95L) that stimulates the immune response and its antitumor activity. In posttransplant lymphoproliferative disorders (PTLDs), we hypothesized that the concentration of sCD95L could exert a biological function and affect clinical outcomes by modulating the immune response. Using the K-VIROGREF biobank, we quantified sCD95L in 163 patients with PTLD, 16 transplant controls, and 28 healthy donors. Transplant recipients had higher plasma levels of sCD95L than healthy donors. More interestingly, patients with PTLD and high concentration of sCD95L had better clinical outcomes than patients with lower concentration, particularly those with central nervous system (CNS) involvement, who are known to have poor survival. At the cellular level, only natural killer and natural killer T-like cell fractions were reduced in the blood of patients with CNS-PTLD and high concentration of sCD95L, suggesting that sCD95L may either promote the trafficking of these cells within tumors or modulate their differentiation/survival. In conclusion, we showed in this exploratory analysis that plasma concentration of sCD95L might be a prognostic marker in patients with PTLD, particularly in those with CNS involvement.