The impact of morbid obesity and weight loss on the immune microenvironment of the endometrium

A Naqvi, Michelle Mackintosh, Abigail Derbyshire, Anna Maria Tsakiroglou, T Walker, Rhona J McVey, J Bolton, Martin Fergie, Steven Bagley, Garry Ashton, Phillip Pemberton, Akheel Syed, Basil Ammori, RJ Byers, Emma Crosbie

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

Background: Endometrial cancer (EC) has strongest association with obesity of all cancers; a 1.60-fold greater risk is conferred per 5kg/m2 increase in body mass index (BMI). Similarly, surgically induced weight loss reduces risk by up to 81%. It is proposed that this association is related to changes in the microenvironment. Although the immune microenvironment has been previously described in normal and neoplastic endometrium, no study has established if it is altered by weight loss.Methods: Samples from a previous prospective study of morbidly obese patients undergoing bariatric surgery were utilised. 43 patients, ages 24-60, were included with three successive biopsies: at surgery, two-months and 12-months. Bloods were taken to collect further clinical data. Patients were predominantly pre-menopausal (37/43) with mean baseline BMI of 52.2 (SD=7.2). Multiplex immunofluorescence was used to simultaneously identify cells positive for markers CD8, CD68, CD3, FOXP3, PD1 and CD56. Primary outcomes were quantity of cells at each time point, repeated measures correlation with weight loss and with systemic inflammatory markers.results: Mean weight loss over 12-months was 29.2kg (SD=12.6). CD8+ (p=0.015, r=-0.32) cell density increased significantly over the 12-months. There was a significant reduction in inflammatory biomarkers CRP (p=1.38x10-5, r=0.58) and IL-6 (p=0.00082, r=0.46). CD3+ density negatively correlated with IL-6 levels (p=0.0028; r =-0.4896).Conclusion: CD8+ cell density in the endometrium increased with surgical weight loss. CD3+ cell density rose, inverse to the fall in IL-6. This supports previous literature on EC immune microenvironments, suggesting these cells play a protective role in the endometrium. It may suggest the inflammatory state seen in obesity downregulates the immune system, as do tumours. These findings could have clinical impact in the development of prognostic biomarkers in EC or immunotherapy targets.
Original languageEnglish
Title of host publicationJournal of Pathology
Volume249
DOIs
Publication statusPublished - 2019

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute

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