Related Experiment Video
Updated: Jul 31, 2025
06:16
Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
12.8K
TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Max Heiduk1,2, Anna Klimova2, Charlotte Reiche1
1Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Summary
In pancreatic cancer, inhibitory immune checkpoint receptors (ICR) like PD-1 and TIGIT on T cells reveal distinct functions. High PD-1/low TIGIT T cells show anti-tumor activity, while blood ICR levels predict patient survival.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immunotherapy has transformed cancer treatment but shows limited efficacy in pancreatic ductal adenocarcinoma (PDAC).
- Investigating inhibitory immune checkpoint receptors (ICR) on T cells is crucial for understanding PDAC's T-cell-mediated antitumor immunity.
Purpose of the Study:
- To analyze the expression of PD-1 and TIGIT on intratumoral and circulating T cells in PDAC patients.
- To associate ICR expression with T-cell differentiation, tumor reactivity, and cytokine profiles.
- To evaluate the prognostic value of ICR expression in PDAC.
Main Methods:
- Multicolor flow cytometry was used to analyze T cells from blood (n=144) and tumor samples (n=107) of PDAC patients.
- Expression of PD-1 and TIGIT was determined on CD8+ T cells, conventional CD4+ T cells (Tconv), and regulatory T cells (Treg).
- Associations with T-cell phenotypes, cytokine expression, and clinical outcomes were assessed, with follow-up for survival analysis.
Main Results:
- Intratumoral T cells exhibited higher PD-1 and TIGIT expression compared to circulating T cells.
- PD-1+TIGIT- T cells showed proinflammatory and tumor-reactive phenotypes, while TIGIT+ T cells displayed anti-inflammatory and exhausted characteristics.
- Intratumoral PD-1+TIGIT- Tconv cells correlated with improved outcomes, whereas high blood ICR levels indicated a worse prognosis for overall survival.
Conclusions:
- PD-1 and TIGIT expression define distinct intratumoral T-cell phenotypes associated with clinical outcomes in PDAC.
- TIGIT is particularly relevant for future PDAC immunotherapeutic strategies.
- ICR expression in peripheral blood serves as a valuable biomarker for patient stratification in PDAC.
