Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2020-10-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001113.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846172571433697280 |
|---|---|
| author | Haidong Dong Svetomir N Markovic Aaron S Mansfield Jacob J Orme Elizabeth Ann L Enninga Fabrice Lucien-Matteoni Heather Dale Edwin Burgstaler Susan M Harrington Matthew K Ball Sean S Park Mathew S Block Yiyi Yan Roxana S Dronca Jeffrey L Winters |
| author_facet | Haidong Dong Svetomir N Markovic Aaron S Mansfield Jacob J Orme Elizabeth Ann L Enninga Fabrice Lucien-Matteoni Heather Dale Edwin Burgstaler Susan M Harrington Matthew K Ball Sean S Park Mathew S Block Yiyi Yan Roxana S Dronca Jeffrey L Winters |
| author_sort | Haidong Dong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-12cda94bbdc0496a8a76193abb6aa4f3 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-12cda94bbdc0496a8a76193abb6aa4f32024-11-10T00:30:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001113Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesiclesHaidong Dong0Svetomir N Markovic1Aaron S Mansfield2Jacob J Orme3Elizabeth Ann L Enninga4Fabrice Lucien-Matteoni5Heather Dale6Edwin Burgstaler7Susan M Harrington8Matthew K Ball9Sean S Park10Mathew S Block11Yiyi Yan12Roxana S Dronca13Jeffrey L Winters14Mayo Clinic, Rochester, MN, USAMayo Clinic Rochester, Rochester, Minnesota, USAOncology, Mayo Clinic, Rochester, Minnesota, USA1 Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA2 Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA1Mayo Clinic, Rochester, MN, USA4 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA4 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA3 Department of Urology, Mayo Clinic, Rochester, Minnesota, USA4 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA5 Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA1 Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA1 Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA6 Department of Hematology and Oncology, Mayo Clinic Florida, Jacksonville, Florida, USA4 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USABackground 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.https://jitc.bmj.com/content/8/2/e001113.full |
| spellingShingle | Haidong Dong Svetomir N Markovic Aaron S Mansfield Jacob J Orme Elizabeth Ann L Enninga Fabrice Lucien-Matteoni Heather Dale Edwin Burgstaler Susan M Harrington Matthew K Ball Sean S Park Mathew S Block Yiyi Yan Roxana S Dronca Jeffrey L Winters Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles Journal for ImmunoTherapy of Cancer |
| title | Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles |
| title_full | Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles |
| title_fullStr | Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles |
| title_full_unstemmed | Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles |
| title_short | Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles |
| title_sort | therapeutic plasma exchange clears circulating soluble pd l1 and pd l1 positive extracellular vesicles |
| url | https://jitc.bmj.com/content/8/2/e001113.full |
| work_keys_str_mv | AT haidongdong therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT svetomirnmarkovic therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT aaronsmansfield therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT jacobjorme therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT elizabethannlenninga therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT fabricelucienmatteoni therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT heatherdale therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT edwinburgstaler therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT susanmharrington therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT matthewkball therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT seanspark therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT mathewsblock therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT yiyiyan therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT roxanasdronca therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles AT jeffreylwinters therapeuticplasmaexchangeclearscirculatingsolublepdl1andpdl1positiveextracellularvesicles |