Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles

• DOI: 10.1136/jitc-2020-001113
• Publication Date: 2020-08-18T06:34:01Z
• Authors: Jacob J Orme; Elizabeth Ann L E...; Fabrice Lucien-Ma...; Heather Dale; Edwin Burgstaler; Susan M Harrington; Matthew K Ball; Aaron S Mansfield; Sean S Park; Mathew S Block; Svetomir N Markovic; Yiyi Yan; Haidong Dong; Roxana S Dronca; Jeffrey L Winters
• Keywords: Clinical/Translational Cancer Immunotherapy; Adult; Male; Plasma Exchange; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Middle Aged; B7-H1 Antigen; 3. Good health; Extracellular Vesicles; 03 medical and health sciences; 0302 clinical medicine; Humans; Female; Immunotherapy; RC254-282; Aged

BackgroundTrans-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.ResultsIn 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.ConclusionHere, 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.