A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα)
<b>Background and Aims:</b> The macrophage “don’t eat me” pathway CD47/SIRPα is a target for promising new immunotherapy. We hypothesized that a soluble variant of SIRPα is present in the blood and may function as a biomarker. <b>Methods:</b> Monocyte derived macrophages (MDM...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/7/937 |
| _version_ | 1797407341729021952 |
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| author | Yoanna V. Vladimirova Marie K. Mølmer Kristian W. Antonsen Niels Møller Nikolaj Rittig Marlene C. Nielsen Holger J. Møller |
| author_facet | Yoanna V. Vladimirova Marie K. Mølmer Kristian W. Antonsen Niels Møller Nikolaj Rittig Marlene C. Nielsen Holger J. Møller |
| author_sort | Yoanna V. Vladimirova |
| collection | DOAJ |
| description | <b>Background and Aims:</b> The macrophage “don’t eat me” pathway CD47/SIRPα is a target for promising new immunotherapy. We hypothesized that a soluble variant of SIRPα is present in the blood and may function as a biomarker. <b>Methods:</b> Monocyte derived macrophages (MDMs) from human buffy-coats were stimulated into macrophage subtypes by LPS and IFN-γ (M1), IL-4 and IL-13 (M2a), IL-10 (M2c) and investigated using flow cytometry. Soluble SIRPα (sSIRPα) was measured in cell cultures and serum by Western blotting and an optimized ELISA. Serum samples were obtained from 120 healthy individuals and from 8 individuals challenged by an LPS injection. <b>Results:</b> All macrophage phenotypes expressed SIRPα by flowcytometry, and sSIRPα was present in all culture supernatants including unstimulated cells. M1 macrophages expressed the lowest level of SIRPαand released the highest level of sSIRPα (<i>p</i> < 0.05). In vivo, the serum level of sSIRPα increased significantly (<i>p</i> < 0.0001) after an LPS challenge in humans. The median concentration in healthy individuals was 28.7 µg/L (19.8–41.1, 95% reference interval), and 20.5 µg/L in an IFCC certified serum reference material. The protein was stable in serum for prolonged storage and repeated freeze/thawing. <b>Conclusions:</b> We demonstrate that sSIRPα is produced constitutively and the concentration increases upon macrophage activation both in vitro and in vivo. It is present in human serum where it may function as a biomarker for the activity of tumor-associated macrophages (TAMs), and for monitoring the effect of immunotherapy. |
| first_indexed | 2024-03-09T03:39:57Z |
| format | Article |
| id | doaj.art-f94275654d9d4646b2cdbfea30a2a833 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T03:39:57Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f94275654d9d4646b2cdbfea30a2a8332023-12-03T14:43:28ZengMDPI AGBiomolecules2218-273X2022-07-0112793710.3390/biom12070937A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα)Yoanna V. Vladimirova0Marie K. Mølmer1Kristian W. Antonsen2Niels Møller3Nikolaj Rittig4Marlene C. Nielsen5Holger J. Møller6Department of Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, DenmarkDepartment of Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, DenmarkDepartment of Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, DenmarkDepartment of Endocrinology and Internal Medicine, Medical/Steno Research Laboratories, Aarhus University Hospital, 8200 Aarhus N, DenmarkDepartment of Endocrinology and Internal Medicine, Medical/Steno Research Laboratories, Aarhus University Hospital, 8200 Aarhus N, DenmarkDepartment of Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, DenmarkDepartment of Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, Denmark<b>Background and Aims:</b> The macrophage “don’t eat me” pathway CD47/SIRPα is a target for promising new immunotherapy. We hypothesized that a soluble variant of SIRPα is present in the blood and may function as a biomarker. <b>Methods:</b> Monocyte derived macrophages (MDMs) from human buffy-coats were stimulated into macrophage subtypes by LPS and IFN-γ (M1), IL-4 and IL-13 (M2a), IL-10 (M2c) and investigated using flow cytometry. Soluble SIRPα (sSIRPα) was measured in cell cultures and serum by Western blotting and an optimized ELISA. Serum samples were obtained from 120 healthy individuals and from 8 individuals challenged by an LPS injection. <b>Results:</b> All macrophage phenotypes expressed SIRPα by flowcytometry, and sSIRPα was present in all culture supernatants including unstimulated cells. M1 macrophages expressed the lowest level of SIRPαand released the highest level of sSIRPα (<i>p</i> < 0.05). In vivo, the serum level of sSIRPα increased significantly (<i>p</i> < 0.0001) after an LPS challenge in humans. The median concentration in healthy individuals was 28.7 µg/L (19.8–41.1, 95% reference interval), and 20.5 µg/L in an IFCC certified serum reference material. The protein was stable in serum for prolonged storage and repeated freeze/thawing. <b>Conclusions:</b> We demonstrate that sSIRPα is produced constitutively and the concentration increases upon macrophage activation both in vitro and in vivo. It is present in human serum where it may function as a biomarker for the activity of tumor-associated macrophages (TAMs), and for monitoring the effect of immunotherapy.https://www.mdpi.com/2218-273X/12/7/937macrophageimmunotherapybiomarkerSIRPαCD47checkpoint |
| spellingShingle | Yoanna V. Vladimirova Marie K. Mølmer Kristian W. Antonsen Niels Møller Nikolaj Rittig Marlene C. Nielsen Holger J. Møller A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα) Biomolecules macrophage immunotherapy biomarker SIRPα CD47 checkpoint |
| title | A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα) |
| title_full | A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα) |
| title_fullStr | A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα) |
| title_full_unstemmed | A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα) |
| title_short | A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα) |
| title_sort | new serum macrophage checkpoint biomarker for innate immunotherapy soluble signal regulatory protein alpha ssirpα |
| topic | macrophage immunotherapy biomarker SIRPα CD47 checkpoint |
| url | https://www.mdpi.com/2218-273X/12/7/937 |
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