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

Jacob J. Orme, Elizabeth Ann L. Enninga, Fabrice Lucien-Matteoni, 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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Article numbere001113
JournalJournal for ImmunoTherapy of Cancer
Issue number2
StatePublished - Aug 17 2020


  • immunotherapy
  • programmed cell death 1 receptor
  • receptors, immunologic
  • translational medical research
  • tumor escape

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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