@article {Ormee001113, author = {Jacob J Orme and Elizabeth Ann L Enninga and Fabrice Lucien-Matteoni and Heather Dale and Edwin Burgstaler and Susan M Harrington and Matthew K Ball and Aaron S Mansfield and Sean S Park and Mathew S Block and Svetomir N Markovic and Yiyi Yan and Haidong Dong and Roxana S Dronca and Jeffrey L Winters}, title = {Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles}, volume = {8}, number = {2}, elocation-id = {e001113}, year = {2020}, doi = {10.1136/jitc-2020-001113}, publisher = {BMJ Specialist Journals}, abstract = {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.}, URL = {https://jitc.bmj.com/content/8/2/e001113}, eprint = {https://jitc.bmj.com/content/8/2/e001113.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }