Jagatia, Ravi;
Doornebal, Ewald J;
Rastovic, Una;
Harris, Nicola;
Feyide, Moyosoreoluwa;
Lyons, Anabel Martinez;
Miquel, Rosa;
... Palma, Elena; + view all
(2023)
Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing.
eBioMedicine
, 97
, Article 104826. 10.1016/j.ebiom.2023.104826.
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Abstract
Background: The exploitation of anti-tumour immunity, harnessed through immunomodulatory therapies, has fundamentally changed the treatment of primary liver cancer (PLC). However, this has posed significant challenges in preclinical research. Novel immunologically relevant models for PLC are urgently required to improve the translation from bench to bedside and back, explore and predict effective combinatorial therapies, aid novel drug discovery and develop personalised treatment modalities. / Methods: We used human precision-cut tissue slices (PCTS) derived from resected tumours to create a patient-specific immunocompetent disease model that captures the multifaceted and intricate heterogeneity of the tumour and the tumour microenvironment. Tissue architecture, tumour viability and treatment response to single agent and combination therapies were assessed longitudinally over 8 days of ex vivo culture by histological analysis, detection of proliferation/cell death markers, ATP content via HPLC. Immune cell infiltrate was assessed using PCR and immunofluorescence. Checkpoint receptor expression was quantified via Quantigene RNA assay. / Findings: After optimising the culture conditions, PCTS maintained the original tissue architecture, including tumour morphology, stroma and tumour-infiltrated leukocytes. Moreover, PCTS retained the tumour-specific immunophenotype over time, suggesting the utility of PCTS to investigate immunotherapeutic drug efficacy and identify non-responsiveness. / Interpretation: Here we have characterised the PCTS model and demonstrated its effectiveness as a robust preclinical tool that will significantly support the development of successful (immuno)therapeutic strategies for PLC. / Funding: Foundation for Liver Research, London.
| Type: | Article |
|---|---|
| Title: | Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ebiom.2023.104826 |
| Publisher version: | https://doi.org/10.1016/j.ebiom.2023.104826 |
| Language: | English |
| Additional information: | Copyright © 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Hepatocellular carcinoma, Intrahepatic cholangiocarcinoma, Immune checkpoint, Tumour culture, Immunotherapy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10178723 |
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