The CD49b (ITGA2) Collagen Receptor Excludes CD8+ T Cell Infiltration in Pancreatic Ductal Adenocarcinoma (PDAC)

PDAC is characterized by a dense desmoplastic stroma, contributing to tumor progression and immune evasion. This study investigates the functional role of CD49b in modulating anti-tumor immune responses and collagen architecture in PDAC. CD49b demonstrated a high tumor-specific expression compared to normal pancreatic tissues and peripheral blood mononuclear cells. Loss of CD49b impaired PDAC cell adhesion to collagen, suppressed and delayed the tumor growth, and enhanced CD8+ T cell infiltration. In vivo depletion of CD8 T cells rescued the tumor growth in CD49b knock-out tumors. CD49b-knockout tumors showed increased secretion of CXCL10 chemokine, which drives T cell chemotaxis, while FAK signaling was downregulated. FAK overexpression restored tumor growth. CD49b knockout changed alignment of collagen fibers which was associated with a microenvironment permissive to immune infiltration. Targeting of CD49b with Vatelizumab disrupted PDAC cell adhesion and reduced tumor progression while increasing CD8+ T cells infiltration. CD49b is a key regulator of collagen-mediated immune interactions in PDAC, and these results support its potential as a therapeutic target.