Sialylated IgG in epithelial cancers inhibits antitumor function of T cells via Siglec‐7

Although effective, immune checkpoint blockade induces response in only a subset of cancer patients. There is an urgent need to discover new immune checkpoint targets. Recently, it was found that a class of sialic acid–binding immunoglobulin‐like lectins (Siglecs) expressed on the surface of T cells in cancer patients inhibit T cell activation through their intracellular immunosuppressive motifs by recognizing sialic acid–carrying glycans, sialoglycans. However, ligands of Siglecs remain elusive. Here, we report sialylated IgG (SIA‐IgG), a ligand to Siglec‐7, that is highly expressed in epithelial cancer cells. SIA‐IgG binds Siglec‐7 directly and inhibits TCR signals. Blocking of either SIA‐IgG or Siglec‐7 elicited potent antitumor immunity in T cells. Our study suggests that blocking of Siglec‐7/SIA‐IgG offers an opportunity to enhance immune function while simultaneously sensitizing cancer cells to immune attack.