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Published on: March 5, 2010
CD24 Is a Potential Immunotherapeutic Target for Mantle Cell Lymphoma
Jimena Álvarez Freile1, Natasha Ustyanovska Avtenyuk1, Macarena González Corrales1
1Department of Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Insights
CD24 acts as an immune checkpoint in mantle cell lymphoma (MCL), showing high expression linked to poor survival. CD24 antibody treatment effectively eliminates MCL cells, suggesting it as a potential therapeutic target for this lymphoma subtype.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- The CD24-Siglec-10 axis is an innate immune checkpoint in carcinoma.
- Investigating CD24 as a therapeutic target in B-cell lymphomas is crucial.
Purpose of the Study:
- To assess CD24 expression in lymphoma.
- To evaluate CD24 antibody treatment's phagocytic effects compared to CD47.
- To determine CD24's clinical relevance in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).
Main Methods:
- Assessed CD24 and CD47 mRNA expression in MCL, follicular lymphoma, and DLBCL patient samples.
- Correlated expression with patient survival data.
- Treated MCL cell lines and primary cells with CD24 and CD47 antibodies.
- Evaluated antibody-induced phagocytosis and its mechanisms (ADCP-dependent or independent).
Main Results:
- High CD24 mRNA expression correlated with poor survival in MCL and follicular lymphoma, unlike CD47.
- CD24 expression did not correlate with survival in DLBCL, whereas CD47 did.
- CD24 antibody treatment potently induced phagocytosis of MCL cells, superior to CD47 blockade.
- CD24 antibody treatment was less effective than CD47 blockade in DLBCL.
- CD24 clone SN3-induced phagocytosis was partly independent of ADCP, suggesting direct checkpoint blockade.
Conclusions:
- CD24 is a potential immunotherapeutic target for MCL, but not DLBCL.
- The CD24-Siglec-10 axis represents a distinct immune checkpoint in MCL.
- Differential efficacy of CD24 and CD47 blockade highlights subtype-specific therapeutic strategies.
Abstract:
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.
