| First Author | Wang J | Year | 2019 |
| Journal | Nat Med | Volume | 25 |
| Issue | 4 | Pages | 656-666 |
| PubMed ID | 30833750 | Mgi Jnum | J:291407 |
| Mgi Id | MGI:6444934 | Doi | 10.1038/s41591-019-0374-x |
| Citation | Wang J, et al. (2019) Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat Med 25(4):656-666 |
| abstractText | Overexpression of the B7-H1 (PD-L1) molecule in the tumor microenvironment (TME) is a major immune evasion mechanism in some patients with cancer, and antibody blockade of the B7-H1/PD-1 interaction can normalize compromised immunity without excessive side-effects. Using a genome-scale T cell activity array, we identified Siglec-15 as a critical immune suppressor. While only expressed on some myeloid cells normally, Siglec-15 is broadly upregulated on human cancer cells and tumor-infiltrating myeloid cells, and its expression is mutually exclusive to B7-H1, partially due to its induction by macrophage colony-stimulating factor and downregulation by IFN-gamma. We demonstrate that Siglec-15 suppresses antigen-specific T cell responses in vitro and in vivo. Genetic ablation or antibody blockade of Siglec-15 amplifies anti-tumor immunity in the TME and inhibits tumor growth in some mouse models. Taken together, our results support Siglec-15 as a potential target for normalization cancer immunotherapy. |
