TY - JOUR T1 - Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-001113 VL - 8 IS - 2 SP - e001113 AU - Jacob J Orme AU - Elizabeth Ann L Enninga AU - Fabrice Lucien-Matteoni AU - Heather Dale AU - Edwin Burgstaler AU - Susan M Harrington AU - Matthew K Ball AU - Aaron S Mansfield AU - Sean S Park AU - Mathew S Block AU - Svetomir N Markovic AU - Yiyi Yan AU - Haidong Dong AU - Roxana S Dronca AU - Jeffrey L Winters Y1 - 2020/08/01 UR - http://jitc.bmj.com/content/8/2/e001113.abstract N2 - Background Trans-acting programmed death-ligand 1 (PD-L1) derives from malignant cells in three known forms. High levels of secreted splice variant PD-L1 (sPD-L1), ADAM10/ADAM17-shed sPD-L1, and PD-L1-positive extracellular vesicles (evPD-L1) each predict poor prognosis and limited response to PD-(L)1 checkpoint inhibitors in cancer. To our knowledge, no clinical intervention has reduced any of these circulating forms of extracellular PD-L1. Here, we explore therapeutic plasma exchange (TPE) as a treatment to reduce circulating extracellular PD-L1.Results In patients with melanoma, sPD-L1 levels above 0.277 ng/mL predicted inferior overall survival. In patients undergoing TPE for non-malignant indications, each TPE session removed a mean 70.8% sPD-L1 and 73.1% evPD-L1 detectable in plasma. TPE also reduced total and ADAM10-positive extracellular vesicles.Conclusion Here, we report the first known clinical intervention to remove either sPD-L1 or evPD-L1 from plasma in vivo. TPE reduces plasma sPD-L1 and evPD-L1 in vivo and may have a role in treatment with immunotherapy. TPE may also prove useful in patients with other extracellular vesicle-related conditions. ER -