ECE2020 Oral Communications Endocrine-related Cancer (7 abstracts)
The role of the tumour microenvironment in pituitary adenoma angiogenesis
Pedro Marques 1 , Sayka Barry 1 , Eivind Carlsen 2 , David Collier 1 , Amy Ronaldson 1 , Sherine Awad 1 , Nigel Mendoza 3 , Samiul Muquit 4 , Neil Dorward 5 , Joan Grieve 5 , Frances Balkwill 6 , Ashley B Grossman 1 & Marta Korbonits 1
1William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK, Centre for Endocrinology, London, United Kingdom; 2STHF, Skien, Norway, Department of Pathology, Skien, Norway; 3Imperial College Healthcare NHS Trust, London, UK, Department of Neurosurgery, London, United Kingdom; 4Derriford Hospital, Plymouth, UK, Department of Neurosurgery, Plymouth, United Kingdom; 5The National Hospital for Neurology and Neurosurgery, UCLH, NHS Trust, London, UK, Department of Neurosurgery, London, United Kingdom; 6Barts Cancer Institute, Queen Mary University of London, UK, London, United Kingdom
Introduction: Angiogenesis is regulated by different components of the tumour microenvironment (TME) including cytokines and immune cells. Although angiogenesis has been studied in pituitary adenomas (PAs), the role of individual TME components in PA angiogenesis remains largely unknown. We aimed to characterise the role of the TME components in determining the angiogenesis of PAs, focusing on PA-infiltrating immune cells and the PA-derived cytokine network.
Methods: Different immune cells were studied by immunohistochemistry in 24 human PAs (16 non-functioning PAs (NFPAs) and 8 somatotrophinomas): macrophages (CD68), M2-macrophages (CD163), M1-macrophages (HLA-DR), cytotoxic T lymphocytes (CD8), T helper lymphocytes (CD4), T regulatory cells (FOXP3), B cells (CD20) and neutrophils (neutrophil elastase); endothelial cells were assessed with CD31. Five normal pituitary samples (NP) were included for comparison. Microvessel density and vascular morphological parameters were estimated with ImageJ software. Cytokine secretome from these same 24 human PAs were assessed on primary cell culture supernatants using a multiplex immunoassay panel with 42 cytokines.
Results: PAs contained 4× more CD68 + macrophages than NP, with a 3-fold increased M2:M1 macrophage ratio, as well as more CD4 + T cells but fewer CD8 + T cells or neutrophils. Microvessel density and microvessel area were higher in NP than PAs, which also had more round and regular vessels. NFPAs had vessels of increased caliber (higher perimeter and Feret’s diameter), occupying an increased area comparing to somatotrophinomas. PAs with more macrophages tended to have higher microvessel density and area, as well as a higher perimeter and Feret’s diameter. The M2:M1 macrophage ratio correlated with microvessel density (P = 0.015) and microvessel area (P < 0.001) in PAs. PAs with more CD4 + T cells had higher microvessel area (P = 0.035), while PAs with more FOXP3 + cells were associated with lower microvessel density (P = 0.021). PAs with more B cells had more rounded vessels (P = 0.021). Of the studied PA-derived cytokines and growth factors, only FGF-2 and CXCL10 were significantly associated with microvessel architecture, namely vessel perimeter (r = –0.407; P = 0.048) and area occupied per vessel (r = 0.407; P = 0.049), respectively.
Conclusions: Our data suggest that different TME components may influence the angiogenesis of PAs: M2-macrophages appears to play a relevant role in PA angiogenesis, and B, CD4 + and FOXP3 + lymphocytes may also have a modulatory role in the PA neovascularisation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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