- Title
- Prognostic role of immune checkpoint regulators in cholangiocarcinoma : a pilot study
- Creator
- Cao, Lu; Prithviraj, Prashanth; Shrestha, Ritu; Sharma, Revati; Kannourakis, George
- Date
- 2021
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/177852
- Identifier
- vital:15343
- Identifier
-
https://doi.org/10.3390/jcm10102191
- Identifier
- ISBN:2077-0383 (ISSN)
- Abstract
- Cholangiocarcinoma (CCA) is a hepatobiliary malignancy associated with steadily increasing incidence and poor prognosis. Ongoing clinical trials are assessing the effectiveness and safety of a few immune checkpoint inhibitors (ICIs) in CCA patients. However, these ICI treatments as monotherapies may be effective for a proportion of patients with CCA. The prevalence and distribution of other immune checkpoints (ICs) in CCA remain unclear. In this pilot study, we screened databases of CCA patients for the expression of 19 ICs and assessed the prognostic significance of these ICs in CCA patients. Notably, expression of immune modulator IDO1 and PD-L1 were linked with poor overall survival, while FASLG and NT5E were related to both worse overall survival and progression-free survival. We also identified immune modulators IDO1, FASLG, CD80, HAVCR2, NT5E, CTLA-4, LGALS9, VTCN1 and TNFRSF14 that synergized with PD-L1 and correlated with worse patient outcomes. In vitro studies revealed that the expression of ICs was closely linked with aggressive CCA subpopulations, such as cancer stem cells and cells undergoing TGF-β and TNF-α-mediated epithelial-to-mesenchymal transition. These findings suggest that the aforementioned IC molecules may serve as potential prognostic biomarkers and drug targets in CCA patients, leading to lasting and durable treatment outcomes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Prashanth Prithviraj, Revati Sharma, George Kannourakis” is provided in this record**
- Publisher
- MDPI
- Relation
- Journal of Clinical Medicine Vol. 10, no. 10 (2021), p.
- Rights
- All metadata describing materials held in, or linked to, the repository is freely available under a CC0 licence
- Rights
- https://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland
- Rights
- Open Access
- Subject
- 1103 Clinical Sciences; Cancer stem cells; CD73; Cholangiocarcinoma; EMT; Galectin-9; IDO1; Immune checkpoints; PD-L1
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