CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma
CD24 and its ligand Siglec-10 were described as an innate immune checkpoint in carcinoma. Here, we investigated this axis in B-cell lymphoma by assessing CD24 expression and evaluating pro-phagocytic effects of CD24 antibody treatment in comparison to hallmark immune checkpoint CD47. In mantle cell...
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MDPI AG
2022-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/5/1175 |
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| author | Jimena Álvarez Freile Natasha Ustyanovska Avtenyuk Macarena González Corrales Harm Jan Lourens Gerwin Huls Tom van Meerten Ewa Cendrowicz Edwin Bremer |
| author_facet | Jimena Álvarez Freile Natasha Ustyanovska Avtenyuk Macarena González Corrales Harm Jan Lourens Gerwin Huls Tom van Meerten Ewa Cendrowicz Edwin Bremer |
| author_sort | Jimena Álvarez Freile |
| collection | DOAJ |
| description | CD24 and its ligand Siglec-10 were described as an innate immune checkpoint in carcinoma. Here, we investigated this axis in B-cell lymphoma by assessing CD24 expression and evaluating pro-phagocytic effects of CD24 antibody treatment in comparison to hallmark immune checkpoint CD47. In mantle cell lymphoma (MCL) and follicular lymphoma patients, high mRNA expression of CD24 correlated with poor overall survival, whereas CD47 expression did not. Conversely, CD24 expression did not correlate with survival in diffuse large B-cell lymphoma (DLBCL), whereas CD47 did. CD24 was also highly expressed on MCL cell lines, where treatment with CD24 antibody clones SN3 or ML5 potently induced phagocytosis, with SN3 yielding >90% removal of MCL cells and triggering phagocytosis of primary patient-derived MCL cells by autologous macrophages. Treatment with CD24 mAb was superior to CD47 mAb in MCL and was comparable in magnitude to the effect observed in carcinoma lines. Reversely, CD24 mAb treatment was less effective than CD47 mAb treatment in DLBCL. Finally, phagocytic activity of clone SN3 appeared at least partly independent of antibody-dependent cellular phagocytosis (ADCP), suggesting CD24/Siglec-10 checkpoint activity, whereas clone ML5 solely induced ADCP. In conclusion, CD24 is an immunotherapeutic target of potential clinical relevance for MCL, but not DLBCL. |
| first_indexed | 2024-03-10T03:16:15Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T03:16:15Z |
| publishDate | 2022-05-01 |
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| series | Biomedicines |
| spelling | doaj.art-1da5f0a70400457ca37c839a7d7747c62023-11-23T10:12:09ZengMDPI AGBiomedicines2227-90592022-05-01105117510.3390/biomedicines10051175CD24 Is a Potential Immunotherapeutic Target for Mantle Cell LymphomaJimena Álvarez Freile0Natasha Ustyanovska Avtenyuk1Macarena González Corrales2Harm Jan Lourens3Gerwin Huls4Tom van Meerten5Ewa Cendrowicz6Edwin Bremer7Department of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsCD24 and its ligand Siglec-10 were described as an innate immune checkpoint in carcinoma. Here, we investigated this axis in B-cell lymphoma by assessing CD24 expression and evaluating pro-phagocytic effects of CD24 antibody treatment in comparison to hallmark immune checkpoint CD47. In mantle cell lymphoma (MCL) and follicular lymphoma patients, high mRNA expression of CD24 correlated with poor overall survival, whereas CD47 expression did not. Conversely, CD24 expression did not correlate with survival in diffuse large B-cell lymphoma (DLBCL), whereas CD47 did. CD24 was also highly expressed on MCL cell lines, where treatment with CD24 antibody clones SN3 or ML5 potently induced phagocytosis, with SN3 yielding >90% removal of MCL cells and triggering phagocytosis of primary patient-derived MCL cells by autologous macrophages. Treatment with CD24 mAb was superior to CD47 mAb in MCL and was comparable in magnitude to the effect observed in carcinoma lines. Reversely, CD24 mAb treatment was less effective than CD47 mAb treatment in DLBCL. Finally, phagocytic activity of clone SN3 appeared at least partly independent of antibody-dependent cellular phagocytosis (ADCP), suggesting CD24/Siglec-10 checkpoint activity, whereas clone ML5 solely induced ADCP. In conclusion, CD24 is an immunotherapeutic target of potential clinical relevance for MCL, but not DLBCL.https://www.mdpi.com/2227-9059/10/5/1175mantle cell lymphomaCD24immunotherapyimmune checkpointphagocytosis |
| spellingShingle | Jimena Álvarez Freile Natasha Ustyanovska Avtenyuk Macarena González Corrales Harm Jan Lourens Gerwin Huls Tom van Meerten Ewa Cendrowicz Edwin Bremer CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma Biomedicines mantle cell lymphoma CD24 immunotherapy immune checkpoint phagocytosis |
| title | CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma |
| title_full | CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma |
| title_fullStr | CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma |
| title_full_unstemmed | CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma |
| title_short | CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma |
| title_sort | cd24 is a potential immunotherapeutic target for mantle cell lymphoma |
| topic | mantle cell lymphoma CD24 immunotherapy immune checkpoint phagocytosis |
| url | https://www.mdpi.com/2227-9059/10/5/1175 |
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