Pilot Data Suggest That Obesity and Presence of Malignancy Are Associated with Altered Immune Cell Infiltration in Endometrial Biopsies

(1) <b>Background</b>: The worldwide endometrial cancer (EC) incidence is rising, amongst others linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, possibly due to low-grade adipose tissue inflammation. We studied immune cell infiltration in the endometrium in relation to diagnosis and obesity. (2) <b>Methods</b>: A cohort was created (<i>n</i> = 44) from postmenopausal women, lean (<i>n</i> = 15) and obese (<i>n</i> = 29), with bleeding complaints due to EC (<i>n</i> = 18) or benign pathology (<i>n</i> = 26). Endometrial biopsies were used to study the immune microenvironment and stained for macrophages (CD68 and CD163), T-cells (CD3 and CD8), and NK-cells (CD56). (3) <b>Results</b>: Malignant samples showed reduced intraepithelial CD3+ and CD8+ T-cells and increased stromal CD3+ T-cells. In obese patients, increased intraepithelial CD3+ and CD8+ T-cells were detected, especially in obese patients with T2DM. Epithelial CD56+ NK-cells were depleted in EC; however, no effect of obesity on NK-cell infiltration was observed. Stromal CD68+ cells were reduced in EC patients, whereas the CD163+ cells were increased. (4) <b>Conclusions</b>: Obesity and malignancy are associated with differences in immune cell presence. The alterations in immune cell infiltration seen in obese EC patients with and without diabetes suggest a complex interaction where obesity-related low-grade inflammation plays a central role.