Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway
Abstract Even with recent advances in therapy regimen, multiple myeloma patients commonly develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1 axis has been demonstrated in pre-clinical models. Monotherapy with PD-1 inhibitors produced disappointing results, but combination...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-03-01
|
| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-018-0589-1 |
| _version_ | 1819064109639925760 |
|---|---|
| author | Rosemarie Tremblay-LeMay Nasrin Rastgoo Hong Chang |
| author_facet | Rosemarie Tremblay-LeMay Nasrin Rastgoo Hong Chang |
| author_sort | Rosemarie Tremblay-LeMay |
| collection | DOAJ |
| description | Abstract Even with recent advances in therapy regimen, multiple myeloma patients commonly develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1 axis has been demonstrated in pre-clinical models. Monotherapy with PD-1 inhibitors produced disappointing results, but combinations with other drugs used in the treatment of multiple myeloma seemed promising, and clinical trials are ongoing. However, there have recently been concerns about the safety of PD-1 and PD-L1 inhibitors combined with immunomodulators in the treatment of multiple myeloma, and several trials have been suspended. There is therefore a need for alternative combinations of drugs or different approaches to target this pathway. Protein expression of PD-L1 on cancer cells, including in multiple myeloma, has been associated with intrinsic aggressive features independent of immune evasion mechanisms, thereby providing a rationale for the adoption of new strategies directly targeting PD-L1 protein expression. Drugs modulating the transcriptional and post-transcriptional regulation of PD-L1 could represent new therapeutic strategies for the treatment of multiple myeloma, help potentiate the action of other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the potentially problematic combination with immunomodulators. This review will focus on the pathophysiology of PD-L1 expression in multiple myeloma and drugs that have been shown to modulate this expression. |
| first_indexed | 2024-12-21T15:25:21Z |
| format | Article |
| id | doaj.art-9742b974e87f424e9309268b742a91ad |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-21T15:25:21Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-9742b974e87f424e9309268b742a91ad2022-12-21T18:58:55ZengBMCJournal of Hematology & Oncology1756-87222018-03-0111111610.1186/s13045-018-0589-1Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathwayRosemarie Tremblay-LeMay0Nasrin Rastgoo1Hong Chang2Laboratory Hematology/Laboratory Medicine Program, University Health Network, University of TorontoDivision of Molecular and Cellular Biology, Toronto General Research InstituteLaboratory Hematology/Laboratory Medicine Program, University Health Network, University of TorontoAbstract Even with recent advances in therapy regimen, multiple myeloma patients commonly develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1 axis has been demonstrated in pre-clinical models. Monotherapy with PD-1 inhibitors produced disappointing results, but combinations with other drugs used in the treatment of multiple myeloma seemed promising, and clinical trials are ongoing. However, there have recently been concerns about the safety of PD-1 and PD-L1 inhibitors combined with immunomodulators in the treatment of multiple myeloma, and several trials have been suspended. There is therefore a need for alternative combinations of drugs or different approaches to target this pathway. Protein expression of PD-L1 on cancer cells, including in multiple myeloma, has been associated with intrinsic aggressive features independent of immune evasion mechanisms, thereby providing a rationale for the adoption of new strategies directly targeting PD-L1 protein expression. Drugs modulating the transcriptional and post-transcriptional regulation of PD-L1 could represent new therapeutic strategies for the treatment of multiple myeloma, help potentiate the action of other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the potentially problematic combination with immunomodulators. This review will focus on the pathophysiology of PD-L1 expression in multiple myeloma and drugs that have been shown to modulate this expression.http://link.springer.com/article/10.1186/s13045-018-0589-1Immune checkpoint inhibitorsPD-L1PD-1Multiple myelomaHistone deacetylaseBromodomain and extraterminal inhibitors |
| spellingShingle | Rosemarie Tremblay-LeMay Nasrin Rastgoo Hong Chang Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway Journal of Hematology & Oncology Immune checkpoint inhibitors PD-L1 PD-1 Multiple myeloma Histone deacetylase Bromodomain and extraterminal inhibitors |
| title | Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway |
| title_full | Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway |
| title_fullStr | Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway |
| title_full_unstemmed | Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway |
| title_short | Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway |
| title_sort | modulating pd l1 expression in multiple myeloma an alternative strategy to target the pd 1 pd l1 pathway |
| topic | Immune checkpoint inhibitors PD-L1 PD-1 Multiple myeloma Histone deacetylase Bromodomain and extraterminal inhibitors |
| url | http://link.springer.com/article/10.1186/s13045-018-0589-1 |
| work_keys_str_mv | AT rosemarietremblaylemay modulatingpdl1expressioninmultiplemyelomaanalternativestrategytotargetthepd1pdl1pathway AT nasrinrastgoo modulatingpdl1expressioninmultiplemyelomaanalternativestrategytotargetthepd1pdl1pathway AT hongchang modulatingpdl1expressioninmultiplemyelomaanalternativestrategytotargetthepd1pdl1pathway |