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Protein-level profiling of TIGIT axis components in human PDAC reveals immune-suppressive expression patterns
D Quatannens1, Y Verhoeven1, S van der Heijden1
1Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, Belgium.
Cancer Immunology, Immunotherapy : CII
|March 10, 2026
Summary
Immune checkpoint TIGIT is upregulated in pancreatic cancer, suggesting dual TIGIT/PD-1 blockade may overcome immune suppression. Restoring DNAM-1 signaling is also crucial for effective immunotherapy in PDAC patients.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immune checkpoint inhibitors show limited efficacy in pancreatic ductal adenocarcinoma (PDAC).
- The role of the TIGIT immune checkpoint axis in PDAC is underexplored.
- Understanding immunosuppressive mechanisms is key for developing effective PDAC therapies.
Purpose of the Study:
- To characterize TIGIT axis components on protein level in PDAC.
- To investigate the relationship between TIGIT and PD-1/PD-L1 expression.
- To identify strategies for immune checkpoint co-targeting in PDAC.
Main Methods:
- Analysis of matched blood and tumor samples from PDAC patients.
- Flow cytometry to assess TIGIT, DNAM-1, TACTILE, and PD-1 expression on immune cells.
- Immunohistochemistry for ligand analysis (CD111, CD112, CD113, CD155).
- RNA expression analysis (TCGA/GTEx) for ligand distribution and gene profiles.
Main Results:
- TIGIT was highly upregulated on intratumoral CD8+ T cells and regulatory T cells (Tregs), often co-expressed with PD-1.
- DNAM-1 expression was reduced in tumors, but uniquely upregulated on Tregs within the PDAC tumor microenvironment (TME).
- CD112 and CD155 ligands were broadly expressed, with novel stromal CD112 localization.
- Intratumoral NK cells were scarce, correlating with DNAM-1 downregulation.
Conclusions:
- TIGIT is a promising immunotherapeutic target in PDAC.
- Dual checkpoint blockade (TIGIT/PD-1) combined with DNAM-1 signaling restoration may overcome PDAC immune suppression.
- These findings provide a mechanistic basis for future clinical trials in PDAC.
