The pancreatic tumor microenvironment of treatment-naïve patients causes a functional shift in γδ T cells, impairing their anti-tumoral defense
2
Issued Date
2025-01-01
Resource Type
ISSN
21624011
eISSN
2162402X
Scopus ID
2-s2.0-85218009881
Journal Title
OncoImmunology
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
OncoImmunology Vol.14 No.1 (2025)
Suggested Citation
Lo Presti E., Cupaioli F., Scimeca D., Unti E., Di Martino V., Daidone R., Amata M., Scibetta N., Soucie E., Meraviglia S., Iovanna J., Dusetti N., De Gaetano A., Merelli I., Di Mitri R. The pancreatic tumor microenvironment of treatment-naïve patients causes a functional shift in γδ T cells, impairing their anti-tumoral defense. OncoImmunology Vol.14 No.1 (2025). doi:10.1080/2162402X.2025.2466301 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/105449
Title
The pancreatic tumor microenvironment of treatment-naïve patients causes a functional shift in γδ T cells, impairing their anti-tumoral defense
Corresponding Author(s)
Other Contributor(s)
Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents a unique challenge for researchers due to its late diagnosis caused by vague symptoms and lack of early detection markers. Additionally, PDAC is characterized by an immunosuppressive microenvironment (TME), making it a difficult tumor to treat. While γδ T cells have shown potential for anti-tumor activity, conflicting studies exist regarding their effectiveness in pancreatic cancer. This study aims to explore the hypothesis that the PDAC TME hinders the anti-tumor capabilities of γδ T cells through blockade of cytotoxic functions. For this reason, we chose to enroll PDAC treatment-naive patients to avoid the possibility of therapy modifying the TME. By flow cytometry, our research findings indicate that the presence of γδ T cells among CD45+ cells in tumor tissue is lower compared to CD66+ cells, but higher than in blood. Circulating Vδ1 T cells exhibit a terminal effector memory phenotype (TEMRA) more than Vδ2 T cells. Interestingly, Vδ1 and Vδ2 T cells appear to be more prevalent at different stages of tumor development. In our in vitro culture using conditioned medium derived from Patient-derived organoids;(PDOs), we observed a shift in expression markers in γδ T cells of healthy individuals toward an activation and exhaustion phenotype, as confirmed by scRNA-seq analysis extracted from a public database. A deeper understanding of γδ T cells in PDAC could be valuable for developing novel therapies aimed at mitigating the impact of the pancreatic tumor microenvironment on this cell population.