Abstract：
: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-γ. 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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Wang J,Sun J,Liu LN,Flies DB,Nie X,Toki M,Zhang J,Song C,Zarr M,Zhou X,Han X,Archer KA,O'Neill T,Herbst RS,Boto AN,Sanmamed MF,Langermann S,Rimm DL,Chen Ldoi
10.1038/s41591-019-0374-xsubject
Has Abstractpub_date
2019-04-01 00:00:00pages
656-666issue
4eissn
1078-8956issn
1546-170Xpii
10.1038/s41591-019-0374-xjournal_volume
25pub_type
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