Inhibition of Stroma-Driven T-cell Exclusion and Exhaustion in Pancreatic Ductal Adenocarcinoma via CXCR4 and PD-1 Inhibition

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Pancreatic ductal adenocarcinoma (PDAC) features a highly immunosuppressive tumor microenvironment that drives T-cell dysfunction.
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3D PDAC spheroids with pancreatic stellate cells create a fibrotic barrier that restricts T-cell infiltration and mimics the desmoplastic TME.
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Infiltrated T-cells in PDAC exhibit an exhaustion signature, with increased expression of PD-1, LAG-3, and CTLA-4.
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Pharmacological blockade of CXCR4 enhances T-cell infiltration, while anti-PD-1 treatment partially restores T-cell effector function.
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Patient-derived spheroids replicate patient-specific T-cell suppression patterns, highlighting their relevance for studying immunotherapy responses.

Frontiers In Immunology

by Alina Deipenbrock, Lina Hofer, Ben E. Wilmes, Timur Cetin, Irene Esposito, Dirk Weyhe, Johannes Stegmaier, Nicole E. Teusch
July 21, 2026

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