Exosomes, PD-L1 and aGvHD: Perspectives for WJMSCmediated Therapy

Abstract

Tumor-derived small extracellular vesicles or exosomes which carry the checkpoint PD-L1 are directly involved in immune evasion and uncontrolled tumor growth. We have recently reported that PD-L1 is also enriched on Wharton's Jelly Mesenchymal Stromal Cell (WJMSC)-associated exosomes [1]. This biological property is likely associated with the physiologic role of WJMSCs at the maternal-fetal interface. These cells have been shown to protect the developing fetus from attack by the maternal immune system due to the foreign paternal antigens which the fetus express. In this manuscript, we review the important roles of exosome-enriched PD-L1 (exo-PD-L1) during WJMSCmediated therapy for acute graft-versus-host disease (aGvHD). We focus on exo-PD-L1's immunomodulation on T cell receptor (TCR) signaling in CD4+ T cells. In addition, we extend our discussions to other exosomeassociated immune regulators, highlighting the potential to develop a cell-free, WJMSC-derived exosome therapy to treat complex immune diseases.