Single-cell RNA sequencing of orthotopic pancreasic cancer reveals characterization of tumor microenvironment by treatment of anti-VSIG4 antibodies in KPC cell transplantation mouse model

However, their efficacy varies substantially among tumor types and is particularly limited in immunologically “cold” malignancies such as pancreatic ductal adenocarcinoma. These tumors exhibit minimal T-cell infiltration and a profoundly immunosuppressive tumor microenvironment (TME), leading to poor responses to ICB.

VSIG4 is a B7-related transmembrane protein highly expressed by tissue-resident macrophages. Previous studies have shown that VSIG4 suppresses proinflammatory macrophage polarization by modulating pyruvate metabolism and enhances M2-like states via lactate-STAT3 signaling and fatty acid oxidation. VSIG4 also inhibits T-cell activation and proliferation, making it a candidate immune checkpoint molecule.