Estrogen receptor α expression in tumor-infiltrating lymphocytes from patients with endometrial cancer.

The complex crosstalk between the tumor milieu, including the hormonal environment and immune system interactions, is important to tumor growth in endometrial cancer (EC). Estradiol-mediated estrogen receptor α (ERα) signaling is critical for the function of regulatory tumor-infiltrating lymphocytes (TILs) in patients with cervical cancer. Therefore, the present study investigated the relative ERα level in infiltrating lymphocytes derived from EC tissues and whether its variable expression is associated with clinicopathological features, including the molecular classification. Endometrial tumor and normal endometrium samples were collected from 82 patients diagnosed with EC; however, only 54 samples were assessed as sufficient and qualified for further study. The frequency of T helper lymphocytes (Th cells), cytotoxic T lymphocytes (CTLs) and B lymphocytes (B cells) as well as the percentages of these cells expressing ERα were examined using flow cytometry. Furthermore, the expression of ERα in these TIL subpopulations was evaluated using median fluorescence intensity (MFI) to assess the absolute level of ERα in the studied lymphocytes. Associations of ERα levels in TILs with clinicopathological characteristics, including molecular subtypes, were measured. All the studied TIL subpopulations showed a significantly lower ERα level compared with normal endometrial tissue, which constituted the control group. However, the frequencies of Th cells and Th cells expressing ERα were significantly increased, while the frequencies of CTLs and CTLs expressing ERα were significantly decreased in EC compared with the control. The frequency of B cells expressing ERα was significantly increased in high grade EC tumors and tumors harboring mismatch repair deficiency. ERα expression (demonstrated with MFI) on examined TIL subsets was negatively correlated with body mass index in patients but did not demonstrate other correlations with the examined clinicopathological prognostic factors. The mechanism of ERα decrease in TILs from endometrial tumors as well as its prognostic significance and potential role in therapeutic targeting needs further investigation, including further examination of its molecular background and functional validation experiments.