CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies
In multiple myeloma (MM), the anti-CD38 monoclonal antibody Daratumumab has become essential in the therapeutic arsenal, although very few predictive factors of response to Daratumumab have been identified in clinical studies. We have prospectively collected biological data from 97 patients treated...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2532226 |
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| author | Djamila Chemlal Camille Pochard Valentin Jacquier Angélique Bruyer Ludovic Gabellier Léa Fornero Clément Vempère Amélie Machura Guilhem Requirand Nicolas Robert Caroline Bret Guillaume Cartron Laure Vincent Hugues de Boussac Jérôme Moreaux Charles Herbaux |
| author_facet | Djamila Chemlal Camille Pochard Valentin Jacquier Angélique Bruyer Ludovic Gabellier Léa Fornero Clément Vempère Amélie Machura Guilhem Requirand Nicolas Robert Caroline Bret Guillaume Cartron Laure Vincent Hugues de Boussac Jérôme Moreaux Charles Herbaux |
| author_sort | Djamila Chemlal |
| collection | DOAJ |
| description | In multiple myeloma (MM), the anti-CD38 monoclonal antibody Daratumumab has become essential in the therapeutic arsenal, although very few predictive factors of response to Daratumumab have been identified in clinical studies. We have prospectively collected biological data from 97 patients treated with Daratumumab in first line or at relapse in our center between 2016 and 2020. These data included multiparameter flow cytometry phenotype (CD200, CD117, CD56, CD38, CD45, and CD27), cytogenetic, and transcriptomic gene expression profiling (GEP) of tumor plasma cells before treatment with Daratumumab. We first looked for predictive factors of response to Daratumumab. We found that high CD56 expression and CD45 expression were significantly associated with better progression free survival (PFS) whereas high CD200 expression was significantly associated with poorer PFS. Then, we showed that the CD200-CD200R immune synapse is responsible for a decrease in Daratumumab response through the alteration of NK cells’ activity. Finally, we demonstrated that inhibition of CD200 increase response to Daratumumab in MM patient samples, highlighting its potential as a predictive biomarker for Daratumumab response and as a possible therapeutic target in combination with Daratumumab. This study is the first to identify phenotypic and molecular factors’ predictor of response to Daratumumab. |
| format | Article |
| id | doaj-art-193341b7d3db4d838f33ee858b38e962 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-193341b7d3db4d838f33ee858b38e9622025-08-20T03:51:19ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2532226CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodiesDjamila Chemlal0Camille Pochard1Valentin Jacquier2Angélique Bruyer3Ludovic Gabellier4Léa Fornero5Clément Vempère6Amélie Machura7Guilhem Requirand8Nicolas Robert9Caroline Bret10Guillaume Cartron11Laure Vincent12Hugues de Boussac13Jérôme Moreaux14Charles Herbaux15Diag2Tec, Montpellier, FranceDepartment of Clinical Hematology, CHU Montpellier Montpellier, FranceInstitute of Human Genetics, Unité Mixte de Recherche Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier, FranceDiag2Tec, Montpellier, FranceDepartment of Clinical Hematology, CHU Montpellier Montpellier, FranceDepartment of Clinical Hematology, CHU Montpellier Montpellier, FranceDiag2Tec, Montpellier, FranceDiag2Tec, Montpellier, FranceDepartment of Biological Hematology, CHU Montpellier Montpellier, FranceDepartment of Biological Hematology, CHU Montpellier Montpellier, FranceInstitute of Human Genetics, Unité Mixte de Recherche Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier, FranceDepartment of Clinical Hematology, CHU Montpellier Montpellier, FranceDepartment of Clinical Hematology, CHU Montpellier Montpellier, FranceDiag2Tec, Montpellier, FranceInstitute of Human Genetics, Unité Mixte de Recherche Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier, FranceInstitute of Human Genetics, Unité Mixte de Recherche Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier, FranceIn multiple myeloma (MM), the anti-CD38 monoclonal antibody Daratumumab has become essential in the therapeutic arsenal, although very few predictive factors of response to Daratumumab have been identified in clinical studies. We have prospectively collected biological data from 97 patients treated with Daratumumab in first line or at relapse in our center between 2016 and 2020. These data included multiparameter flow cytometry phenotype (CD200, CD117, CD56, CD38, CD45, and CD27), cytogenetic, and transcriptomic gene expression profiling (GEP) of tumor plasma cells before treatment with Daratumumab. We first looked for predictive factors of response to Daratumumab. We found that high CD56 expression and CD45 expression were significantly associated with better progression free survival (PFS) whereas high CD200 expression was significantly associated with poorer PFS. Then, we showed that the CD200-CD200R immune synapse is responsible for a decrease in Daratumumab response through the alteration of NK cells’ activity. Finally, we demonstrated that inhibition of CD200 increase response to Daratumumab in MM patient samples, highlighting its potential as a predictive biomarker for Daratumumab response and as a possible therapeutic target in combination with Daratumumab. This study is the first to identify phenotypic and molecular factors’ predictor of response to Daratumumab.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2532226MyelomaimmunotherapiesresistanceCD200 |
| spellingShingle | Djamila Chemlal Camille Pochard Valentin Jacquier Angélique Bruyer Ludovic Gabellier Léa Fornero Clément Vempère Amélie Machura Guilhem Requirand Nicolas Robert Caroline Bret Guillaume Cartron Laure Vincent Hugues de Boussac Jérôme Moreaux Charles Herbaux CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies OncoImmunology Myeloma immunotherapies resistance CD200 |
| title | CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies |
| title_full | CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies |
| title_fullStr | CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies |
| title_full_unstemmed | CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies |
| title_short | CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies |
| title_sort | cd200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti cd38 monoclonal antibodies |
| topic | Myeloma immunotherapies resistance CD200 |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2532226 |
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