| 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
|
| Resource |
| Human and Animal Cells |
KG-1a(RCB1928)
SLVL(RCB1702) |
