Reference - Detail
| RRC ID | 85083 |
|---|---|
| Author | Li J, Wang Z, Qin X, Zhong MC, Tang Z, Qian J, Dou J, Hussell T, King PD, Nunès JA, Yamanashi Y, Davidson D, Veillette A. |
| Title | CD200R1-CD200 checkpoint inhibits phagocytosis differently from SIRPα-CD47 to suppress tumor growth. |
| Journal | Nat Commun |
| Abstract |
Targeting macrophage inhibitory receptors like signal regulatory protein α (SIRPα) is a promising avenue in cancer treatment. Whereas the ligand of SIRPα, CD47, is widely expressed on tumor cells, its simultaneous presence on all normal cells raises concerns about toxicity and efficacy. This study identifies CD200R1, which binds CD200 on specific tumor types and limited normal cells, as an alternative inhibitory checkpoint for phagocytosis. Blocking or removing CD200R1 from macrophages or CD200 from tumor cells increases phagocytosis and suppresses tumor growth. In humans, CD200R1 is mainly expressed in immunosuppressive macrophages and is induced by interleukin-4. Unlike SIRPα that utilizes phosphatases Src homology 2 domain phosphatase (SHP)-1 and SHP-2, CD200R1 mediates its inhibitory effect via the kinase Csk. Combined CD200R1-CD200 and SIRPα-CD47 blockade further boosts phagocytosis and reduces tumor growth of CD200-expressing tumors, compared to either blockade alone. Thus, targeting CD200R1-CD200 is a promising strategy for immune checkpoint blockade in macrophages, either alone or alongside blockade of other checkpoints. |
| Volume | 16(1) |
| Pages | 5145 |
| Published | 2025-6-3 |
| DOI | 10.1038/s41467-025-60456-3 |
| PII | 10.1038/s41467-025-60456-3 |
| PMID | 40461553 |
| PMC | PMC12134331 |
| MeSH | Animals Antigens, CD* / genetics Antigens, CD* / immunology Antigens, CD* / metabolism Antigens, Differentiation* / metabolism CD47 Antigen* / immunology CD47 Antigen* / metabolism Cell Line, Tumor Female Humans Macrophages / immunology Macrophages / metabolism Mice Mice, Inbred C57BL Neoplasms* / immunology Neoplasms* / pathology Orexin Receptors Phagocytosis* / drug effects Phagocytosis* / immunology Receptors, Cell Surface* / genetics Receptors, Cell Surface* / immunology Receptors, Cell Surface* / metabolism Receptors, Immunologic* / genetics Receptors, Immunologic* / immunology Receptors, Immunologic* / metabolism |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 15 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | KG-1a(RCB1928) SLVL(RCB1702) |