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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number909180
JournalFrontiers in Endocrinology
Volume13
DOIs
Publication statusPublished - 13 Jul 2022

Keywords

  • ex vivo model
  • immune checkpoint receptor
  • neuroendocrine liver metastases
  • soluble immunomodulators
  • tissue slices
  • tumour modeling

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