CD274 and pancreatic ductal adenocarcinoma: This fibrotic stroma poses a physical barrier to drug penetration and fosters a hypoxic, nutrient-poor microenvironment that further compromises anti-tumor immunity.14 Given these challenges, dual inhibition of the PD-L1 pathway (to reinvigorate T cells) and the TGF-β pathway (to alleviate TME immunosuppression and stromal barriers) has emerged as a rationally designed and highly promising treatment strategy for pancreatic ductal adenocarcinoma, with the potential to overcome the limitations of single-agent checkpoint inhibitors.