Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer.

ABSTRACT: Tumor-associated macrophages (TAM) in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) exhibit immunosuppressive phenotypes and impaired phagocytic activity, facilitating tumor progression and immune evasion. In this study, we identified integrin α3β1, composed of ITGA3 and ITGB1 subunits, as a sialylated glycoprotein ligand for Siglec-10, an inhibitory glyco-immune checkpoint receptor highly expressed on TAMs in PDAC. The interaction between Siglec-10 on TAMs and α3β1 on PDAC cells suppressed macrophage-mediated phagocytosis, thereby promoting immune evasion. Consistently, disrupting Siglec-10 interactions using mAbs significantly enhanced macrophage phagocytosis of PDAC cells and alleviated myeloid cell-mediated inhibition of T-cell proliferation and activation in

SUBMITTER: Saini P 

PROVIDER: S-EPMC12671567 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature