Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment
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 clinic...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.909180/full |
| _version_ | 1828265813110423552 |
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| author | Ewald Jan Doornebal Ewald Jan Doornebal Nicola Harris Nicola Harris Antonio Riva Antonio Riva Ravi Jagatia 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 John Ramage Elena Palma Elena Palma Rajaventhan Srirajaskanthan Rajaventhan Srirajaskanthan Shilpa Chokshi Shilpa Chokshi |
| author_facet | Ewald Jan Doornebal Ewald Jan Doornebal Nicola Harris Nicola Harris Antonio Riva Antonio Riva Ravi Jagatia 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 John Ramage Elena Palma Elena Palma Rajaventhan Srirajaskanthan Rajaventhan Srirajaskanthan Shilpa Chokshi Shilpa Chokshi |
| author_sort | Ewald Jan Doornebal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T04:44:19Z |
| format | Article |
| id | doaj.art-79a575480fcb4a9381354a424b03a91e |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T04:44:19Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-79a575480fcb4a9381354a424b03a91e2022-12-22T03:01:53ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-07-011310.3389/fendo.2022.909180909180Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour MicroenvironmentEwald Jan Doornebal0Ewald Jan Doornebal1Nicola Harris2Nicola Harris3Antonio Riva4Antonio Riva5Ravi Jagatia6Ravi Jagatia7Michail Pizanias8Andreas Prachalias9Krishna Menon10Melissa Preziosi11Ane Zamalloa12Rosa Miquel13Yoh Zen14Michael Robert Orford15Simon Eaton16Nigel Heaton17John Ramage18John Ramage19Elena Palma20Elena Palma21Rajaventhan Srirajaskanthan22Rajaventhan Srirajaskanthan23Shilpa Chokshi24Shilpa Chokshi25Foundation for Liver Research, The Roger Williams Institute of Hepatology, London, United KingdomKing’s College London, Faculty of Life Sciences and Medicine, London, United KingdomFoundation for Liver Research, The Roger Williams Institute of Hepatology, London, United KingdomKing’s College London, Faculty of Life Sciences and Medicine, London, United KingdomFoundation for Liver Research, The Roger Williams Institute of Hepatology, London, United KingdomKing’s College London, Faculty of Life Sciences and Medicine, London, United KingdomFoundation for Liver Research, The Roger Williams Institute of Hepatology, London, United KingdomKing’s College London, Faculty of Life Sciences and Medicine, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomLiver Histopathology Laboratory, Institute of Liver Studies, King’s College Hospital, London, United KingdomLiver Histopathology Laboratory, Institute of Liver Studies, King’s College Hospital, London, United KingdomGreat Ormond Street Institute of Child Health, University College London, London, United KingdomGreat Ormond Street Institute of Child Health, University College London, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomNeuroendocrine Tumour Unit, ENETS Centre of Excellence, King’s College Hospital, London, United KingdomFoundation for Liver Research, The Roger Williams Institute of Hepatology, London, United KingdomKing’s College London, Faculty of Life Sciences and Medicine, London, United KingdomInstitute of Liver Studies, King’s College Hospital and King’s College London, London, United KingdomNeuroendocrine Tumour Unit, ENETS Centre of Excellence, King’s College Hospital, London, United KingdomFoundation for Liver Research, The Roger Williams Institute of Hepatology, London, United KingdomKing’s College London, Faculty of Life Sciences and Medicine, London, United KingdomNeuroendocrine 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.909180/fulltissue slicesneuroendocrine liver metastasesex vivo modelsoluble immunomodulatorsimmune checkpoint receptortumour modeling |
| spellingShingle | Ewald Jan Doornebal Ewald Jan Doornebal Nicola Harris Nicola Harris Antonio Riva Antonio Riva Ravi Jagatia 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 John Ramage Elena Palma Elena Palma Rajaventhan Srirajaskanthan Rajaventhan Srirajaskanthan Shilpa Chokshi Shilpa Chokshi Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment Frontiers in Endocrinology tissue slices neuroendocrine liver metastases ex vivo model soluble immunomodulators immune checkpoint receptor tumour modeling |
| title | Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment |
| title_full | Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment |
| title_fullStr | Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment |
| title_full_unstemmed | Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment |
| title_short | Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment |
| title_sort | human immunocompetent model of neuroendocrine liver metastases recapitulates patient specific tumour microenvironment |
| topic | tissue slices neuroendocrine liver metastases ex vivo model soluble immunomodulators immune checkpoint receptor tumour modeling |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.909180/full |
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