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Sialylated IgG in epithelial cancers inhibits antitumor function of T cells via Siglecā7
- Source :
- Cancer Science. 114:370-383
- Publication Year :
- 2022
- Publisher :
- Wiley, 2022.
-
Abstract
- 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.
- Subjects :
- Cancer Research
Oncology
General Medicine
Subjects
Details
- ISSN :
- 13497006 and 13479032
- Volume :
- 114
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....cd45ab7fe812209a10579347b4f6dc20