| First Author | Wang C | Year | 2023 |
| Journal | Nature | Volume | 621 |
| Issue | 7980 | Pages | 830-839 |
| PubMed ID | 37674079 | Mgi Jnum | J:345378 |
| Mgi Id | MGI:7595971 | Doi | 10.1038/s41586-023-06511-9 |
| Citation | Wang C, et al. (2023) CD300ld on neutrophils is required for tumour-driven immune suppression. Nature 621(7980):830-839 |
| abstractText | The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy(1,2). Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance(2-4). Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy. |
