Although prior research has shown that obesity increases the risk for endometrial cancer and that weight loss is protective, the underlying mechanisms are incompletely understood, according to the authors of a study published in the International Journal of Obesity. “Previous work has shown a strong positive correlation between serum levels of pro-inflammatory cytokines and adipokines and endometrial cancer risk,” they wrote. “We hypothesize that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium.”

Based on this hypothesis, the study team aimed to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. They conducted a prospective cohort study of women with class III obesity (BMI ≥ 40 kg/m2) undergoing bariatric surgery or adhering to a medically supervised low-calorie diet. Women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 and 52 kg/m2, respectively.

 

Bariatric Surgery Vs. Low-Calorie Diet

Blood and endometrial samples were collected at baseline, and at 2 and 12 months after weight loss intervention. Serum was analyzed for the inflammatory markers C-reactive protein (CRP), IL-6, and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for the 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.

Weight loss at 12 months was greater in women who received bariatric surgery than in those assigned to a low-calorie diet. There were significant reductions in serum CRP and IL-6, but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss. Tissue CD3+ cell density correlated negatively with systemic IL-6 levels.

 

Weight Loss Linked With Reduced Systemic Inflammation

“The study presents convincing evidence of a change in the immunological landscape of morphologically normal endometrium in women with class III obesity who undergo significant weight loss,” the researchers write. “We observed that 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. These findings indicate that the immunological landscape of the endometrium may be affected by obesity and weight loss, and by extension, that the immune microenvironment may influence susceptibility to neoplastic change.”

If validated in larger studies, the insights provided in this investigation could have important clinical implications, the study authors concluded. “This is the first study, to our knowledge, which compares immune biomarkers in serum and endometrial tissue before and after weight loss in women with class III obesity,” they added. “Immune biomarkers could enable individualized endometrial cancer risk prediction and also measure the success of risk-reducing interventions.”

The study team would like to see future research directed toward encouraging recruitment of protective immune cells to the endometrium to boost the natural clearance of precursor and precancerous lesions. “We urgently need innovative solutions to avert the impending surge of endometrial cancer diagnoses predicted by the escalating global obesity problem,” they wrote.