Novel combination immunotherapy for the treatment of pancreatic ductal adenocarcinoma
(2025)
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Details
- Authors
- Supervisors
- Jacquemin, Patrick
- Abstract
- Cancer immunotherapy seeks to stimulate the immune system to eliminate tumors, but responses remain limited in pancreatic ductal adenocarcinoma (PDAC), which is largely resistant to immune checkpoint inhibitors (ICI) like anti-CTLA-4. VISTA, an emerging checkpoint protein highly expressed in PDAC and regulating both innate and adaptive immunity, may be upregulated as a resistance mechanism to ICIs, making it a promising target. Its co-blockade with CTLA-4 could therefore enhance antitumor immunity. In an orthotopic murine PDAC model, combined anti-VISTA and anti-CTLA-4 treatment cleared tumors in over half of the treated mice, unlike monotherapies, while boosting T cell density and effector activity, raising the CD4/Treg ratio, and promoting a pro-inflammatory tumor microenvironment. Our results show that VISTA/CTLA-4 co-blockade can promote PDAC rejection and warrants clinical evaluation.
- Affiliations
Citations
Wulleman, M. (2025). Novel combination immunotherapy for the treatment of pancreatic ductal adenocarcinoma. https://hdl.handle.net/2078.5/260595