The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy
Open accessAbstract
Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called ‘don’t eat me’ signals—including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of ‘don’t eat me’ signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown ‘don’t eat me’ signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24–Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy. CD24 interacts with the tumour-associated-macrophage receptor Siglec-10 to inhibit the macrophage-mediated clearance of cancer cells, revealing a new ‘don’t eat me’ signal as a potential target for cancer immunotherapy.
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Easy quantitative assessment of genome editing by sequence trace decomposition
Brinkman, E. K., Chen, T., Amendola, M., & van Steensel, B. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku936 · Cited by 2,390
PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Gordon, S. R., Maute, R. L., Dulken, B. W., Hutter, G., George, B. M., McCracken, M. N., Gupta, R., Tsai, J. M., Sinha, R., Corey, D., et al. (2017) · Nature · doi:10.1038/nature22396 · Cited by 2,247
Self-citationMajeti, R., Chao, M. P., Alizadeh, A. A., Pang, W. W., Jaiswal, S., Gibbs, K. D., van Rooijen, N., & Weissman, I. L. (2009) · Cell · doi:10.1016/j.cell.2009.05.045 · Cited by 1,752
Self-citationCD24 and Siglec-10 Selectively Repress Tissue Damage–Induced Immune Responses
Chen, G.-Y., Tang, J., Zheng, P., & Liu, Y. (2009) · Science · doi:10.1126/science.1168988 · Cited by 786
Miksa, M., Komura, H., Wu, R., Shah, K. G., & Wang, P. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2008.11.019 · Cited by 320
Siglec-G/10 in self-nonself discrimination of innate and adaptive immunity
Chen, G.-Y., Brown, N. K., Zheng, P., & Liu, Y. (2014) · Glycobiology · doi:10.1093/glycob/cwu068 · Cited by 90
Cited by
Macrophages as tools and targets in cancer therapy
Mantovani, A., Allavena, P., Marchesi, F., & Garlanda, C. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00520-5 · Cited by 1,807
Immune checkpoint therapy—current perspectives and future directions
Sharma, P., Goswami, S., Raychaudhuri, D., Siddiqui, B. A., Singh, P., Nagarajan, A., Liu, J., Subudhi, S. K., Poon, C., Gant, K. L., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.006 · Cited by 1,206
The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans
The Tabula Sapiens Consortium*, Jones, R. C., Karkanias, J., Krasnow, M. A., Pisco, A. O., Quake, S. R., Salzman, J., Yosef, N., Bulthaup, B., Brown, P., et al. (2022) · Science · doi:10.1126/science.abl4896 · Cited by 1,056
Self-citationClinical relevance of tumour-associated macrophages
Pittet, M. J., Michielin, O., & Migliorini, D. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00620-6 · Cited by 731
TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.013 · Cited by 656
“, 2014), CD24-Siglec10, CD47-SIRPα signaling (Barkal et al., 2019; Iribarren et al., 2018; Veillette and Chen, 2018; Willingham et al., 2012), and CXCR4CXCL12 signaling (Hughes et al.”
Metadata
- Authors
- Barkal, A. A., Brewer, R. E., Markovic, M., Kowarsky, M., Barkal, S. A., Zaro, B. W., Krishnan, V., Hatakeyama, J., Dorigo, O., Barkal, L. J., & Weissman, I. L.
- Venue
- Nature
- Published
- 2019-07-31
- Volume
- 572
- Issue
- 7769
- Pages
- 392-396
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2966214074
- Cited by
- 1,385
- References
- 7
- FWCI
- 41.98
- Type
- journal article
- Language
- en
- Open access
- green
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- Barkal, A. A., Brewer, R. E., Markovic, M., Kowarsky, M., Barkal, S. A., Zaro, B. W., Krishnan, V., Hatakeyama, J., Dorigo, O., Barkal, L. J., & Weissman, I. L. (2019). CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. https://doi.org/10.1038/s41586-019-1456-0
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