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Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment

Authors :
Ewald Jan Doornebal
Nicola Harris
Antonio Riva
Ravi Jagatia
Michail Pizanias
Andreas Prachalias
Krishna Menon
Melissa Preziosi
Ane Zamalloa
Rosa Miquel
Yoh Zen
Michael Robert Orford
Simon Eaton
Nigel Heaton
John Ramage
Elena Palma
Rajaventhan Srirajaskanthan
Shilpa Chokshi
Source :
Frontiers in Endocrinology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

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.

Details

Language :
English
ISSN :
16642392
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Endocrinology
Publication Type :
Academic Journal
Accession number :
edsdoj.79a575480fcb4a9381354a424b03a91e
Document Type :
article
Full Text :
https://doi.org/10.3389/fendo.2022.909180