Sialylated IgG in epithelial cancers inhibits antitumor function of T cells via Siglec-7.
Cancer Sci
; 114(2): 370-383, 2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36310398
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Ácido N-Acetilneuramínico
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China