PD-1 Blockade Aggravates Epstein–Barr Virus+ Post-Transplant Lymphoproliferative Disorder in Humanized Mice Resulting in Central Nervous System Involvement and CD4+ T Cell Dysregulations

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common malignancies after solid organ or allogeneic stem cell transplantation. Most PTLD cases are B neoplasias carrying Epstein-Barr virus (EBV). A therapeutic approach reduction immunosuppression to allow T cells develop and combat EBV. If this not effective, approaches include immunotherapies such as monoclonal antibodies targeting CD20 adoptive cells. Immune checkpoint inhibition (ICI) treat EBV + was established clinically due risks rejection graft- versus -host disease. Previously, blockade programmed death receptor (PD)-1 by a antibody (mAb) during ex vivo infection mononuclear with EBV/M81 strain showed lower xenografted lymphoma development in mice. Subsequently, fully humanized mice infected EBV/B95-8 treated PD-1 blocking mAb aggravation development. Here, we evaluated vis-a-vis infections effects used blocker. Fifteen 17 weeks human CD34 transplantation, Nod.Rag.Gamma were two types laboratory strains expressing firefly luciferase. Dynamic optical imaging analyses systemic triggered vigorous CD8 expansion. Pembrolizumab administered from 2 5 post-infections significantly aggravated spread and, for M81 model, increased mortality ICI promoted Ki67 CD30 EBER PD-L1 central nervous system (CNS) involvement, mirroring CNS humans. associated frequencies circulating blood profound collapse CD4 lymphatic tissues. Mice pembrolizumab an escalation exhausted TIM-3, LAG-3 tissues, higher levels several cytokines plasma high densities FoxP3 regulatory tumor microenvironment. We conclude that acute driving strong priming decompensates towards immunosuppression. Given variety preclinical models available, our conferred cautionary note indicating progression PTLD.