ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P713 | DOI: 10.1530/endoabs.63.P713

Characterizing the microenvironment of pituitary neuroendocrine tumours, new approaches and tools to explore the function and contribution of folliculostellate cells

Mirela Diana Ilie1,2, Marie Chanal1,2, Moitza Principe1,2, Nicolas Gadot3, Alexandre Vasiljevic2,4, Emmanuel Jouanneau2,5, Gérald Raverot1,2,6 & Philippe Bertolino1

1Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR5286, Lyon, France; 2Université Lyon 1, Lyon, France; 3Centre de Recherche en Cancérologie de Lyon, Plateforme Anatomopathologie-Recherche, Lyon, France; 4Centre de Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; 5Service de Neurochirurgie, Hôpital Neurologique, Hospices Civils de Lyon, Bron, France; 6Fédération d’Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.

Background: Tumour microenvironment (TME) can comprise >50% of the tumour mass and includes non-tumour cells like immune cells and fibroblasts, as well as extracellular matrix, signaling molecules, and blood and lymph vessels. In recent years, TME has begun to be considered both a prognostic tool and a therapeutic target. While the existence of TME is well accepted and described in numerous cancers, little is known about the TME of pituitary neuroendocrine tumours (PitNETs). Recent work highlighted the existence of tumour infiltrating lymphocytes and tumour-associated macrophages within PitNETs. Interestingly, besides the above-mentioned populations, folliculostellate cells (FSCs), which are resident cells of the normal anterior pituitary, are also found in PitNETs’ TME.

Hypothesis: Besides the role FSCs have in the normal anterior pituitary, their identification in PitNETs suggests they may have a major implication in these tumours. Therefore, better characterizing PitNET-associated FSCs and understanding their contribution and their functional interactions with tumour cells and tumour-associated stroma may provide important indications regarding the mechanisms that drive tumourigenesis-associated processes.

Materials and methods: Exploration of the histological characteristics of gonadotroph and somatotroph PitNETs through the use of immunostainings of paraffin-embedded tumours, followed by whole slide scanning and automated imaging analysis using a software that allows for single-cell characterization, coupled with the exploration of the cellular properties of PitNETs’ TME through the use of derived FSC cultures from human gonadotroph and somatotroph PitNETs. Correlation of this data with matching histopathological and clinical data.

Results: Single-cell analysis of immunostainings of paraffin-embedded PitNETs is feasible and allows for the quantification and mapping of cells, and for the identification of the clustering of FSCs with other cells. Also, the isolation of PitNET-derived cell lines that have FSC characteristics is feasible from both gonadotroph and somatotroph tumours. Our preliminary analysis highlighted differences between gonadotroph and somatotroph PitNETs, but also intra-tumour heterogeneity concerning the FSCs.

Perspectives: This kind of combined approach will allow us to better characterize FSCs and their heterogeneity in PitNETs. In the future, by deepening these insights and by better understanding the biology of FSCs within the TME, the field will be one step closer to the potential discovery of new diagnostic and prognostic markers and of new and/or personalized treatments.