The CD49b (ITGA2) collagen receptor excludes CD8+ T cell infiltration in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma that promotes tumor progression and immune evasion. We examined how the collagen receptor CD49b (ITGA2) shapes anti-tumor immunity and stromal architecture in PDAC. CD49b was highly expressed in tumors compared with normal pancreas and peripheral blood mononuclear cells. CD49b loss impaired PDAC cell adhesion to collagen, delayed tumor growth, and increased CD8+ T cell infiltration; depletion of CD8+ T cells in vivo restored tumor growth in CD49b knockout tumors. CD49b knockout tumors secreted more CXCL10, a T cell chemoattractant, and showed reduced FAK signaling, while FAK overexpression rescued tumor growth. CD49b loss also altered collagen fiber alignment, generating a microenvironment permissive to immune infiltration. Pharmacological CD49b blockade with vatelizumab disrupted tumor cell adhesion, reduced tumor progression, and enhanced CD8+ T cell infiltration. These findings identify CD49b as a regulator of collagen-mediated immune exclusion in PDAC and support its evaluation as a therapeutic target.