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Conventional therapeutic approaches to post-transplant lymphoproliferative disorder (PTLD) occurring after solid-organ transplantation have shown only limited success in achieving durable response. Key factors driving the pathogenesis of PTLD include Epstein–Barr virus (EBV) reactivation and impaired immune surveillance due to prolonged immune suppression. Thus, EBV-specific cytotoxic T lymphocytes (EBV-CTLs) have emerged as an alternative therapeutic approach for the treatment of EBV-associated PTLD by enhancing EBV-specific immunity. We evaluated the safety and efficacy of EBV latent membrane proteins (LMP)-1- and 2-specific CTLs in two PTLD patients at high risk for relapse. Following diagnosis, patients were initially treated with a combination of chemotherapy and/or radiotherapy. Patients then received a total of eight doses of 2 × 107 EBV-CTLs/m2. Following initial therapy, both patients achieved complete remission confirmed by FDG-PET/CT imaging. Post-remission therapy using adoptive transfer of EBV-CTLs was safe without immediate or late toxicities. Infusion of EBV-CTLs led to an overall reduction in plasma EBV levels in the peripheral blood, which was associated with long-term remission of both patients during a follow-up of more than 65 months. Further prospective studies with larger number of patients will be needed to confirm the role of EBV-CTLs as post-remission therapy in high-risk PTLD.

Mesenchymal stem cells (MSCs) are multipotent stromal cells with the potential to differentiate into different tissue lineages. In addition to their differentiation potential, MSCs possess immunomodulatory properties that have created growing interest in both pre-clinical and clinical research. Over the years, MSCs have been applied rapidly in the clinic in a wide variety of immune-mediated disorders; however, MSC therapy has shown contradictory results, often with poor clinical outcomes. Recently, studies on MSC-based immune modulation have provided possible explanations for the conflicting clinical reports. It is now generally recognized that the immunomodulatory properties of MSCs are not constitutive but are induced by various mediators present in the inflammatory microenvironment. Different inflammatory stimuli are able to polarize MSCs to elicit distinct immunomodulatory phenotypes. Thus, the concepts of plasticity and polarization of MSC-based immune modulation may have important therapeutic implications in the clinic. In this review, we focus on the underlying mechanisms of MSC-mediated immune regulation that contribute to their therapeutic potential. Importantly, we discuss novel strategic approaches that enhance the therapeutic potential of MSCs through a consideration of MSC plasticity in immune modulation.