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

  • Authors:
    • Marcin A. Jedryka
    • Anna Slawek
    • Paulina Kubik
    • Daria Lorek
    • Anna Ewa Kedzierska
    • Andrzej Czekanski
    • Rafał Matkowski
    • Anna Chelmonska-Soyta
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Wroclaw Medical University, 53‑413 Wroclaw, Poland, Laboratory of Reproductive Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53‑114 Wroclaw, Poland
    Copyright: © Jedryka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 83
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    Published online on: December 19, 2025
       https://doi.org/10.3892/ol.2025.15436
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Abstract

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.
View Figures

Figure 1

Representative dot plots for the
gating of T helper lymphocytes
(CD45+CD3+CD4+), cytotoxic T
lymphocytes (CD45+CD3+CD8a+) and B
lymphocytes (CD45+CD3−CD19+) and
representative histograms of the ERα expression (red histograms)
overlayed with the respective isotype-matched controls (blue
histograms) in these cells. ERα, estrogen receptor α.

Figure 2

Frequency of the three studied
subpopulations of tumor-infiltrating lymphocytes, (A) T helper
lymphocytes (CD45+CD3+CD4+), (B)
cytotoxic T lymphocytes
(CD45+CD3+CD8+) and (C) B
lymphocytes (CD45+CD3−CD19+), in
the collected cancer and healthy endometrium samples. The results
were compared using Wilcoxon signed rank test.

Figure 3

Frequency of the three studied
subpopulations of tumor-infiltrating lymphocytes expressing ERα,
(A) T helper lymphocytes expressing ERα
(CD45+CD3+CD4+ERα+),
(B) cytotoxic T lymphocytes expressing ERα
(CD45+CD3+CD8+ERα+) and
(C) B lymphocytes expressing ERα
(CD45+CD3−CD19+ERα+),
in the collected endometrial cancer and healthy endometrium
samples. The results were compared using Wilcoxon signed rank test.
ERα, estrogen receptor α.

Figure 4

Expression of ERα (measured as MFI)
in the three studied tumor infiltrating lymphocyte subpopulations,
(A) T helper lymphocytes
(CD45+CD3+CD4+), (B) cytotoxic T
lymphocytes (CD45+CD3+CD8+) and
(C) B lymphocytes
(CD45+CD3−CD19+), in the collected
endometrial cancer and healthy endometrium samples. The results
were compared using Wilcoxon signed rank test. ERα, estrogen
receptor α; MFI, median fluorescence intensity.

Figure 5

Relationship between the frequency of
the B lymphocyte subset
(CD45+CD3−CD19+) expressing ERα
derived from endometrial cancer tissue and certain prognostic
features: (A) Histological grade, (B) MMR status and (C) TCGA
cluster. The results were compared using Mann-Whitney U test or
Kruskal-Wallis test followed by Dunn test. ERα, estrogen receptor
α; MMR, mismatch repair; MSI, microsatellite instability; NSMP,
non-specific molecular profile; p53, p53 mutated tumors; TCGA, The
Cancer Genome Atlas.

Figure 6

Spearman's ρ coefficient correlation
plot of BMI vs. ERα MFI in the three studied subpopulations of
tumor infiltrating lymphocytes: (A) T helper lymphocytes
(CD45+CD3+CD4+), (B) cytotoxic T
lymphocytes (CD45+CD3+CD8+) and
(C) B lymphocytes
(CD45+CD3−CD19+). BMI, body mass
index; ERα, estrogen receptor α; MFI, median fluorescence
intensity.
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Spandidos Publications style
Jedryka MA, Slawek A, Kubik P, Lorek D, Kedzierska AE, Czekanski A, Matkowski R and Chelmonska-Soyta A: Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer. Oncol Lett 31: 83, 2026.
APA
Jedryka, M.A., Slawek, A., Kubik, P., Lorek, D., Kedzierska, A.E., Czekanski, A. ... Chelmonska-Soyta, A. (2026). Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer. Oncology Letters, 31, 83. https://doi.org/10.3892/ol.2025.15436
MLA
Jedryka, M. A., Slawek, A., Kubik, P., Lorek, D., Kedzierska, A. E., Czekanski, A., Matkowski, R., Chelmonska-Soyta, A."Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer". Oncology Letters 31.2 (2026): 83.
Chicago
Jedryka, M. A., Slawek, A., Kubik, P., Lorek, D., Kedzierska, A. E., Czekanski, A., Matkowski, R., Chelmonska-Soyta, A."Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer". Oncology Letters 31, no. 2 (2026): 83. https://doi.org/10.3892/ol.2025.15436
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Spandidos Publications style
Jedryka MA, Slawek A, Kubik P, Lorek D, Kedzierska AE, Czekanski A, Matkowski R and Chelmonska-Soyta A: Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer. Oncol Lett 31: 83, 2026.
APA
Jedryka, M.A., Slawek, A., Kubik, P., Lorek, D., Kedzierska, A.E., Czekanski, A. ... Chelmonska-Soyta, A. (2026). Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer. Oncology Letters, 31, 83. https://doi.org/10.3892/ol.2025.15436
MLA
Jedryka, M. A., Slawek, A., Kubik, P., Lorek, D., Kedzierska, A. E., Czekanski, A., Matkowski, R., Chelmonska-Soyta, A."Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer". Oncology Letters 31.2 (2026): 83.
Chicago
Jedryka, M. A., Slawek, A., Kubik, P., Lorek, D., Kedzierska, A. E., Czekanski, A., Matkowski, R., Chelmonska-Soyta, A."Estrogen receptor α expression in tumor‑infiltrating lymphocytes from patients with endometrial cancer". Oncology Letters 31, no. 2 (2026): 83. https://doi.org/10.3892/ol.2025.15436
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