Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59
Daratumumab (DARA) has improved the outcome of treatment of multiple myeloma (MM). DARA acts via complement-dependent and -independent mechanisms. Resistance to DARA may result from upregulation of the complement inhibitory proteins CD55 and CD59, downregulation of the DARA target CD38 on myeloma ce...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/21/3365 |
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| author | Kieran Brennan Katrine F. Iversen Alfonso Blanco-Fernández Thomas Lund Torben Plesner Margaret M. Mc Gee |
| author_facet | Kieran Brennan Katrine F. Iversen Alfonso Blanco-Fernández Thomas Lund Torben Plesner Margaret M. Mc Gee |
| author_sort | Kieran Brennan |
| collection | DOAJ |
| description | Daratumumab (DARA) has improved the outcome of treatment of multiple myeloma (MM). DARA acts via complement-dependent and -independent mechanisms. Resistance to DARA may result from upregulation of the complement inhibitory proteins CD55 and CD59, downregulation of the DARA target CD38 on myeloma cells or altered expression of the checkpoint inhibitor ligand programmed death ligand-1 (PD-L1) or other mechanisms. In this study, EVs were isolated from peripheral blood (PB) and bone marrow (BM) from multiple myeloma (MM) patients treated with DARA and PB of healthy controls. EV size and number and the expression of CD38, CD55, CD59 and PD-L1 as well as the EV markers CD9, CD63, CD81, CD147 were determined by flow cytometry. Results reveal that all patient EV samples express CD38, PD-L1, CD55 and CD59. The level of CD55 and CD59 are elevated on MM PB EVs compared with healthy controls, and the level of PD-L1 on MM PB EVs is higher in patients responding to treatment with DARA. CD147, a marker of various aspects of malignant behaviour of cancer cells and a potential target for therapy, was significantly elevated on MM EVs compared with healthy controls. Furthermore, mass spectrometry data suggests that MM PB EVs bind DARA. This study reveals a MM PB and BM EV protein signature that may have diagnostic and prognostic value. |
| first_indexed | 2024-03-09T19:11:27Z |
| format | Article |
| id | doaj.art-89251a82b34b474798955d35adc686e2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T19:11:27Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-89251a82b34b474798955d35adc686e22023-11-24T04:07:30ZengMDPI AGCells2073-44092022-10-011121336510.3390/cells11213365Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59Kieran Brennan0Katrine F. Iversen1Alfonso Blanco-Fernández2Thomas Lund3Torben Plesner4Margaret M. Mc Gee5School of Biomolecular & Biomedical Science, University College Dublin (UCD), Dublin 4, IrelandInstitute of Regional Health Science, University of Southern Denmark, 7100 Vejle, DenmarkFlow Cytometry Core Technology, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD), Belfield, Dublin 4, IrelandDepartment of Hematology, Odense University Hospital, 5000 Odense, DenmarkInstitute of Regional Health Science, University of Southern Denmark, 7100 Vejle, DenmarkSchool of Biomolecular & Biomedical Science, University College Dublin (UCD), Dublin 4, IrelandDaratumumab (DARA) has improved the outcome of treatment of multiple myeloma (MM). DARA acts via complement-dependent and -independent mechanisms. Resistance to DARA may result from upregulation of the complement inhibitory proteins CD55 and CD59, downregulation of the DARA target CD38 on myeloma cells or altered expression of the checkpoint inhibitor ligand programmed death ligand-1 (PD-L1) or other mechanisms. In this study, EVs were isolated from peripheral blood (PB) and bone marrow (BM) from multiple myeloma (MM) patients treated with DARA and PB of healthy controls. EV size and number and the expression of CD38, CD55, CD59 and PD-L1 as well as the EV markers CD9, CD63, CD81, CD147 were determined by flow cytometry. Results reveal that all patient EV samples express CD38, PD-L1, CD55 and CD59. The level of CD55 and CD59 are elevated on MM PB EVs compared with healthy controls, and the level of PD-L1 on MM PB EVs is higher in patients responding to treatment with DARA. CD147, a marker of various aspects of malignant behaviour of cancer cells and a potential target for therapy, was significantly elevated on MM EVs compared with healthy controls. Furthermore, mass spectrometry data suggests that MM PB EVs bind DARA. This study reveals a MM PB and BM EV protein signature that may have diagnostic and prognostic value.https://www.mdpi.com/2073-4409/11/21/3365daratumumabextracellular vesiclesplasmabone marrowmultiple myelomacomplement |
| spellingShingle | Kieran Brennan Katrine F. Iversen Alfonso Blanco-Fernández Thomas Lund Torben Plesner Margaret M. Mc Gee Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59 Cells daratumumab extracellular vesicles plasma bone marrow multiple myeloma complement |
| title | Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59 |
| title_full | Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59 |
| title_fullStr | Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59 |
| title_full_unstemmed | Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59 |
| title_short | Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59 |
| title_sort | extracellular vesicles isolated from plasma of multiple myeloma patients treated with daratumumab express cd38 pd l1 and the complement inhibitory proteins cd55 and cd59 |
| topic | daratumumab extracellular vesicles plasma bone marrow multiple myeloma complement |
| url | https://www.mdpi.com/2073-4409/11/21/3365 |
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