Supplementary Figure 4 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Correlation analysis in TCGA showing associations between ITGA3 or ITGB1 and Siglec-10 and its ligand-forming enzymes (ST3GAL1, B3GNT3)</p>

Supplementary Figure 5 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Flow cytometry and functional assays showing that ITGA3 knockout reduces Siglec-10 binding and that ITGB1 expression enables PDAC cells to evade macrophage-mediated phagocytosis</p>

Supplementary Figure 2 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Flow cytometry analysis showing Siglec-10 expression in monocytes and monocyte-derived macrophages</p>

Supplementary Figure 1 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Schematic and TCGA dataset analysis showing elevated expression of sialyltransferases that generate Siglec-10 ligands in pancreatic cancer compared to normal tissues</p>

Supplementary Figure 3 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Flow cytometry analysis showing high expression of ITGA3 and ITGB1 on PDAC cells</p>

Supplementary Figure 7 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Gating strategy for sorting human tumor-associated macrophages from mouse subcutaneous tumors for RNA-seq analysis</p>

Supplementary Table 1 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Sequences of the monoclonal antibodies against Siglec-10</p>

Supplementary Figure 6 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Flow cytometry analysis showing that anti–Siglec-10 antibodies do not alter ITGA3, ITGB1, or Siglec-10 ligand levels on PDAC cells</p>

Supplementary Figure 8 from Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

2026-01-02

<p>Analysis showing expression of human Siglec-10 on myeloid cells in B-hSIGLEC10 mice compared with C57BL/6 controls</p>

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

2026-01-02

<div>Abstract<p>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 <i>in vitro</i>. In both a xenograft mouse model engrafted with human macrophages and a human Siglec-10 transgenic mouse model, targeting Siglec-10 with mAbs reduced PDAC growth. These findings suggest that Siglec-10 interactions are key mediators of TAM-driven immune evasion in PDAC and highlight the therapeutic potential of targeting these interactions to restore antitumor immunity.</p>Significance:<p>Pancreatic tumor cells exploit integrin α3β1 to engage the immunosuppressive checkpoint receptor Siglec-10 on myeloid cells, driving immune evasion, which can be targeted with antibody-mediated blockade of Siglec-10 to restore antitumor immunity.</p></div>