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Human immunocompetent model of neuroendocrine liver metastases recapitulates patient-specific tumour microenvironment

Doornebal, Ewald; Harris, Nicola; RIVA, Antonio; Jagatia, Ravi; Pizanias, Michail; Prachalias, Andreas; Menon, Krishna; ... Chokshi, Shilpa; + view all (2022) Human immunocompetent model of neuroendocrine liver metastases recapitulates patient-specific tumour microenvironment. Frontiers in Endocrinology 10.3389/fendo.2022.909180. (In press). Green open access

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Abstract

Neuroendocrine liver metastases (LM-NEN) develop in a considerable proportion of patients with gastroenteropancreatic neuroendocrine neoplasms. There is a paucity of experimental models that accurately recapitulate this complex metastatic human liver microenvironment precluding scientific and clinical advancements. Here, we describe the development of a novel personalised immunocompetent precision cut tumour slice (PCTS) model for LM-NEN using resected human liver tissue. The histological assessment throughout the culture demonstrated that slices maintain viability for at least 7 days and retain the cellular heterogeneity of the original tumour. Essential clinical features, such as patient-specific histoarchitecture, tumour grade, neuroendocrine differentiation and metabolic capacity, are preserved in the slices. The PCTS also replicate the tumor-specific immunological profile as shown by the innate and adaptive immunity markers analysis. Furthermore, the study of soluble immune checkpoint receptors in the culture supernatants proves that these immunomodulators are actively produced by LM-NEN and suggests that this process is epithelium-dependent. This model can be employed to investigate these pathways and provides a powerful platform for mechanistic, immunological and pre-clinical studies.

Type: Article
Title: Human immunocompetent model of neuroendocrine liver metastases recapitulates patient-specific tumour microenvironment
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fendo.2022.909180
Publisher version: https://www.frontiersin.org/articles/10.3389/fendo...
Language: English
Additional information: © 2022 Doornebal, Harris, Riva, Pizanias, Prachalias, Menon, Preziosi, Zamalloa, Miquel, Zen, Orford, Eaton, Heaton, Ramage, Palma, Srirajaskanthan and Chokshi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Keywords: Tissue slices, Neuroendocrine liver metastases, Ex vivo model, soluble immunomodulators, immune checkpoint receptors, Tumour modeling
UCL classification: UCL
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
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
URI: https://discovery.ucl.ac.uk/id/eprint/10149871
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