Siglec-15/sialic acid axis as a central glyco-immune checkpoint in breast cancer bone metastasis
Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid-binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs.
| Errataetall: |
CommentIn: Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2400499121. - PMID 38377217 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 5 vom: 30. Jan., Seite e2312929121 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Yixian [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Blocking |
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| Anmerkungen: |
Date Completed 24.01.2024 Date Revised 20.02.2024 published: Print-Electronic CommentIn: Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2400499121. - PMID 38377217 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2312929121 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid-binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs | ||
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| 700 | 1 | |a Yu, Liqun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chenhang |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Haoxue |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yi-Hsuan |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuda |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Han |e verfasserin |4 aut | |
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