| First Author | Weng CH | Year | 2026 |
| Journal | Cell Rep | Volume | 45 |
| Issue | 6 | Pages | 117443 |
| PubMed ID | 42213780 | Mgi Jnum | J:387483 |
| Mgi Id | MGI:8349399 | Doi | 10.1016/j.celrep.2026.117443 |
| Citation | Weng CH, et al. (2026) Tumor-intrinsic expression of signal regulatory protein alpha contributes to the suppression of anti-tumor immune responses. Cell Rep 45(6):117443 |
| abstractText | SIRPalpha is a well-characterized inhibitory receptor on myeloid immune cells. However, human and mouse melanoma cells can also express high levels of SIRPalpha. Whether and how melanoma cell-intrinsic SIRPalpha contributes to tumor progression and anti-tumor immunity remains underexplored. Here, we identify a role of tumor cell-intrinsic SIRPalpha in suppressing immune recruitment and activation. SIRPalpha deletion in melanoma cells enhances tumor control and increases immune infiltration. Transcriptomic analyses reveal that loss of tumor cell-intrinsic SIRPalpha upregulates the chemokine CXCL10 in both human and mouse melanoma cells. Notably, Cxcl10 knockdown in SIRPalpha-deficient melanoma partially rescues tumor growth and reduces CD8(+) T cell infiltration, mirroring the phenotype of SIRPalpha-expressing tumors and indicating that tumor cell-intrinsic SIRPalpha promotes immune evasion by suppressing Cxcl10-mediated T cell recruitment. Our study uncovers an unrecognized mechanism of SIRPalpha-mediated immune suppression and highlights SIRPalpha silencing as a potential therapeutic strategy to enhance immune infiltration and T cell-mediated tumor control across SIRPalpha-expressing cancers. |
