SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity
Since the successful introduction of checkpoint inhibitors targeting the adaptive immune system, monoclonal antibodies inhibiting CD47-SIRPα interaction have shown promise in enhancing anti-tumor treatment efficacy. Apart from SIRPα, neutrophils express a broad repertoire of inhibitory receptors, in...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17141 |
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| author | Panagiota Bouti Colin Blans Bart J. A. M. Klein Debarati Shome Reza Nadafi Michel Van Houdt Karin Schornagel Paul J. J. H. Verkuijlen Virginie Roos Rogier M. Reijmers Robin Van Bruggen Taco W. Kuijpers Hanke L. Matlung |
| author_facet | Panagiota Bouti Colin Blans Bart J. A. M. Klein Debarati Shome Reza Nadafi Michel Van Houdt Karin Schornagel Paul J. J. H. Verkuijlen Virginie Roos Rogier M. Reijmers Robin Van Bruggen Taco W. Kuijpers Hanke L. Matlung |
| author_sort | Panagiota Bouti |
| collection | DOAJ |
| description | Since the successful introduction of checkpoint inhibitors targeting the adaptive immune system, monoclonal antibodies inhibiting CD47-SIRPα interaction have shown promise in enhancing anti-tumor treatment efficacy. Apart from SIRPα, neutrophils express a broad repertoire of inhibitory receptors, including several members of the sialic acid-binding receptor (SIGLEC) family. Here, we demonstrate that interaction between tumor cell-expressed sialic acids and SIGLEC-5/14 on neutrophils inhibits antibody-dependent cellular cytotoxicity (ADCC). We observed that conjugate formation and trogocytosis, both essential processes for neutrophil ADCC, were limited by the sialic acid-SIGLEC-5/14 interaction. During neutrophil-tumor cell conjugate formation, we found that inhibition of the interaction between tumor-expressed sialic acids and SIGLEC-5/14 on neutrophils increased the CD11b/CD18 high affinity conformation. By dynamic acoustic force measurement, the binding between tumor cells and neutrophils was assessed. The interaction between SIGLEC-5/14 and the sialic acids was shown to inhibit the CD11b/CD18-regulated binding between neutrophils and antibody-opsonized tumor cells. Moreover, the interaction between sialic acids and SIGLEC-5/14-consequently hindered trogocytosis and tumor cell killing. In summary, our results provide evidence that the sialic acid-SIGLEC-5/14 interaction is an additional target for innate checkpoint blockade in the tumor microenvironment. |
| first_indexed | 2024-03-08T20:43:01Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:43:01Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b1d02dca3e904f9dba6623f7fca7dc722023-12-22T14:13:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241714110.3390/ijms242417141SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell CytotoxicityPanagiota Bouti0Colin Blans1Bart J. A. M. Klein2Debarati Shome3Reza Nadafi4Michel Van Houdt5Karin Schornagel6Paul J. J. H. Verkuijlen7Virginie Roos8Rogier M. Reijmers9Robin Van Bruggen10Taco W. Kuijpers11Hanke L. Matlung12Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsLUMICKS, Paalbergweg 3, 1105 AG Amsterdam, The NetherlandsLUMICKS, Paalbergweg 3, 1105 AG Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsLUMICKS, Paalbergweg 3, 1105 AG Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsDepartment of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The NetherlandsSince the successful introduction of checkpoint inhibitors targeting the adaptive immune system, monoclonal antibodies inhibiting CD47-SIRPα interaction have shown promise in enhancing anti-tumor treatment efficacy. Apart from SIRPα, neutrophils express a broad repertoire of inhibitory receptors, including several members of the sialic acid-binding receptor (SIGLEC) family. Here, we demonstrate that interaction between tumor cell-expressed sialic acids and SIGLEC-5/14 on neutrophils inhibits antibody-dependent cellular cytotoxicity (ADCC). We observed that conjugate formation and trogocytosis, both essential processes for neutrophil ADCC, were limited by the sialic acid-SIGLEC-5/14 interaction. During neutrophil-tumor cell conjugate formation, we found that inhibition of the interaction between tumor-expressed sialic acids and SIGLEC-5/14 on neutrophils increased the CD11b/CD18 high affinity conformation. By dynamic acoustic force measurement, the binding between tumor cells and neutrophils was assessed. The interaction between SIGLEC-5/14 and the sialic acids was shown to inhibit the CD11b/CD18-regulated binding between neutrophils and antibody-opsonized tumor cells. Moreover, the interaction between sialic acids and SIGLEC-5/14-consequently hindered trogocytosis and tumor cell killing. In summary, our results provide evidence that the sialic acid-SIGLEC-5/14 interaction is an additional target for innate checkpoint blockade in the tumor microenvironment.https://www.mdpi.com/1422-0067/24/24/17141neutrophil ADCCSIGLECsialic acidcheckpoint blockadeantibody therapy |
| spellingShingle | Panagiota Bouti Colin Blans Bart J. A. M. Klein Debarati Shome Reza Nadafi Michel Van Houdt Karin Schornagel Paul J. J. H. Verkuijlen Virginie Roos Rogier M. Reijmers Robin Van Bruggen Taco W. Kuijpers Hanke L. Matlung SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity International Journal of Molecular Sciences neutrophil ADCC SIGLEC sialic acid checkpoint blockade antibody therapy |
| title | SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity |
| title_full | SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity |
| title_fullStr | SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity |
| title_full_unstemmed | SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity |
| title_short | SIGLEC-5/14 Inhibits CD11b/CD18 Integrin Activation and Neutrophil-Mediated Tumor Cell Cytotoxicity |
| title_sort | siglec 5 14 inhibits cd11b cd18 integrin activation and neutrophil mediated tumor cell cytotoxicity |
| topic | neutrophil ADCC SIGLEC sialic acid checkpoint blockade antibody therapy |
| url | https://www.mdpi.com/1422-0067/24/24/17141 |
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