Endocrine Abstracts (2019) 68 OC2 | DOI: 10.1530/endoabs.68.OC2

Development of ex-vivo models of metastatic neuroendocrine neoplasms

Ewald Doornebal1, Nicola Harris1, Helen Edwards1, Rosa Miquel2, Yoh Zen2, Michail Pizanias2, Andreas Prachalias2, Krishna Menon2, Ane Zamalloa2, Melissa Preziosi2, Nigel Heaton2, John K Ramage2, Roger Williams1,2, Elena Palma1, Shilpa Chokshi1 & Raj Srirajaskanthan2

1Institute of Liver Research, London, UK; 2Institute of Liver Studies, London, UK

Background: The lack of relevant in-vivo and in-vitro models has precluded investigations of the pathophysiology of metastatic NENs. Organotypic tumour slices retain the complexity of tumours in-vivo without extensive manipulation of the tissue. The aims of this study are to understand the utility of precision cut slice technology to develop an immunocompetent model of metastatic GEP NENs to test new therapeutics and elucidate immunological, molecular and cellular characteristics.

Methods: To date, 20 participants have been recruited and 5 liver tissue samples, both tumour and surrounding ‘healthy’ liver tissue, have successfully been sliced and cultured for up to 7 days consistently and in some instances up to 15 days. Viability, metabolic activity, immunocompetency and histology have been assessed. Tissue has also been stained for Ki67 and Chromogranin A expression by immunofluorescence at all timepoints. In addition, tumour infiltrating lymphocytes, plasma, matched peripheral blood mononuclear cells, tumour culture supernatants and slice homogenates for RNA/DNA analysis have been collected and stored daily to enable further analysis.

Results: We have demonstrated NET samples can be successfully sliced and cultured for up to 15 days. Histologically the tissue architecture is maintained over the culture period and tissue viability markers (LDH) remain stable. We have confirmed that metabolic activity and innate/adaptive immune signatures are preserved in the slices.

Conclusions: We have successfully developed a personalised ex-vivo model of GEP NENs that retains the structural, metabolic and immunological signatures observed in-vivo.