期刊
FRONTIERS IN ENDOCRINOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.909180
关键词
tissue slices; neuroendocrine liver metastases; ex vivo model; soluble immunomodulators; immune checkpoint receptor; tumour modeling
资金
- Foundation for Liver Research (FLR)
- Neuroendocrine Research Foundation (NETRF)
This article describes the development of a personalised immunocompetent precision cut tumour slice (PCTS) model for neuroendocrine liver metastases (LM-NEN). The model preserves cellular heterogeneity and clinical features of the original tumour and provides a powerful platform for investigating tumor pathways and conducting mechanistic, immunological, and pre-clinical studies.
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.
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