TY - JOUR
T1 - The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium
AU - Naqvi, Anie
AU - MacKintosh, Michelle
AU - Derbyshire, Abigail
AU - Tsakiroglou, Anna Maria
AU - Walker, Thomas
AU - McVey, Rhona J
AU - Bolton, James
AU - Fergie, Martin
AU - Bagley, Steven
AU - Ashton, Garry
AU - Pemberton, Philip W
AU - Syed, Akheel
AU - Ammori, Basil
AU - Byers, Richard
AU - Crosbie, Emma
N1 - Funding Information:
EJC was supported through an National Institute for Health Research (NIHR) Clinician Scientist award (NIHR-CS-012-009). MLM and AED were supported by Manchester University NHS Foundation Trust Clinical Research Fellowships. This article presents independent research funded by the NIHR, supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007) and facilitated by the Greater Manchester Local Clinical Research Network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the study; and decision to submit the study for publication.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/2
Y1 - 2021/12/2
N2 - Background: The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. Methods: We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m
2) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss. Results: Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m
2, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (n = 37, median 63.3 kg) than low-calorie diet (n = 6, median 12.8 kg). There were significant reductions in serum CRP (p = 3.62 × 10
−6, r = 0.570) and IL-6 (p = 0.0003, r = 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (p = 0.0097, r = −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (p = 0.0376; r = −0.318). Conclusion: Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.
AB - Background: The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. Methods: We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m
2) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss. Results: Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m
2, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (n = 37, median 63.3 kg) than low-calorie diet (n = 6, median 12.8 kg). There were significant reductions in serum CRP (p = 3.62 × 10
−6, r = 0.570) and IL-6 (p = 0.0003, r = 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (p = 0.0097, r = −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (p = 0.0376; r = −0.318). Conclusion: Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.
U2 - 10.1038/s41366-021-01027-6
DO - 10.1038/s41366-021-01027-6
M3 - Article
SN - 0307-0565
JO - International Journal of Obesity
JF - International Journal of Obesity
ER -
