Vorinostat restores iNKT cell functionality in aggressive cholangiocarcinoma
4
Issued Date
2025-05-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-86000753020
Journal Title
Biomedicine and Pharmacotherapy
Volume
186
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.186 (2025)
Suggested Citation
Htwe K.S.S., Soontrapa K., Prasopporn S., Chusorn P., Okada S., Jirawatnotai S., Sampattavanich S., Wongkajornsilp A. Vorinostat restores iNKT cell functionality in aggressive cholangiocarcinoma. Biomedicine and Pharmacotherapy Vol.186 (2025). doi:10.1016/j.biopha.2025.117964 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/106787
Title
Vorinostat restores iNKT cell functionality in aggressive cholangiocarcinoma
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
In this study, we explored the potential of histone deacetylase (HDAC) inhibitors, with a focus on Vorinostat, to restore the functionality of invariant natural killer T (iNKT) cells—a unique subset of T cells with potent anti-tumor activity that are often impaired within the tumor microenvironment. Using aggressive cholangiocarcinoma (CCA) cell lines lacking CD1d molecules, we observed a marked decline in iNKT cell reactivity within 48 h of exposure to CCA cells. Through a systematic approach that included the utilization of the L1000FWD search engine, Vorinostat emerged as a promising candidate for mitigating iNKT cell dysfunction. Vorinostat induced significant molecular alterations in iNKT-nonresponsive CCA cells, enhancing CD1d expression, the production of inflammatory cytokines and the activation of T cell receptor (TCR) signaling pathways. These changes effectively reactivated iNKT cells and restored their anti-tumor functionality. In the mouse xenograft model, combined treatment with Vorinostat significantly inhibited tumor growth. These findings suggest that Vorinostat may offer a novel therapeutic strategy for patients with cholangiocarcinoma who are resistant to conventional chemotherapy.