SFEIES24 Oral Communications Oral Communications (10 abstracts)
Multiplex immunofluorescence identifies novel role for STING upregulation in pituitary neuroendocrine tumours
Paul Benjamin Loughrey 1,2 , Aoife McArdle 1 , Hannah James 1 , Kristopher D. McCombe 1 , Fionn Corr 1 , Brian Herron 3 , Ella Ross 1 , Stephen Cooke 4 , Steven J. Hunter 2 , Marta Korbonits 5 , Stephanie G. Craig 1 & Jacqueline A. James 1,3,6
1Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, United Kingdom; 2Regional Centre for Endocrinology and Diabetes, Belfast Health and Social Care Trust, Belfast, United Kingdom; 3Department of Cellular Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom; 4Department of Neurosurgery, Belfast Health and Social Care Trust, Belfast, United Kingdom; 5Centre for Endocrinology, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom; 6Northern Ireland Biobank, Queen’s University Belfast, Belfast, United Kingdom
Background: Pituitary neuroendocrine tumours (PitNETs) have almost invariably benign histopathological characteristics but result in comorbidity and mortality. There has been interest in the composition of the PitNET immune microenvironment, particularly with the advent of immunotherapy-associated hypophysitis linked to PD-L1 and CTLA-4 checkpoint inhibitors. The innate immune cGAS-STING pathway is activated by DNA damage and DNA damage is a known feature of somatotrophinomas. Enhanced understanding of the PitNET immune microenvironment may yield novel biomarkers and therapeutic targets.
Aim: To explore the immune microenvironment composition of functioning PitNETs fulfilling the clinical diagnoses of acromegaly, prolactinoma and thyrotrophinoma using multiplex immunofluorescence and digital image analysis.
Methods: PitNET tissues (growth hormone-secreting n = 63, thyrotrophinoma n=5, prolactinoma n = 11) resected between 01/01/2000-09/07/2019 were retrieved via the Northern Ireland Biobank. Normal pituitary adjacent to Rathke cleft cyst was used as control (n = 4). Samples were stained with two multiplex immunofluorescence panels each containing six biomarkers and scanned using PhenoImager HT. Panel 1: CD3, CD4, CD8, CD20, Ki-67, synaptophysin. Panel 2: CD3, CD68, STING, PD-L1, CTLA-4, synaptophysin. Biomarker quantification was undertaken using QuPath. GraphPad Prism was used for statistical analysis.
Results: PitNETs did not have significantly higher tumour infiltrating CD4+ (p = 0.990), CD8+ (p = 0.567) T lymphocytes or CD20+ B lymphocytes (p = 0.186) compared to normal pituitary. There were significantly higher levels of total CD68+ macrophages (p < 0.001) and CD68+STING+ macrophages (p < 0.001) in PitNETs compared to normal pituitary. There was significantly higher STING expression in tumour cells compared to normal pituitary (p < 0.001).
Conclusions: This is the first time that multiplex immunofluorescence and digital image analysis have successfully been used for simultaneous biomarker quantification in PitNETs. The data indicate that T and B lymphocytes do not play a significant role in PitNETs. However, macrophages and the innate cGAS-STING pathway are upregulated in this cohort of functioning PitNETs and represent novel areas for further investigation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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