Radiat Oncol J.  2021 Dec;39(4):324-333. 10.3857/roj.2021.00472.

Gamma-ray irradiation modulates PGRMC1 expression and the number of CD56+ and FoxP3+ cells in the tumor microenvironment of endometrial endometrioid adenocarcinoma

Affiliations
  • 1Department of Pathology, Gomel State Medical University, Gomel, Belarus
  • 2Department of Obstetrics and Gynecology, Gomel State Medical University, Gomel, Belarus
  • 3Department of Histology, Cytology and Embryology, Gomel State Medical University, Gomel, Belarus
  • 4University Research Laboratory, Gomel State Medical University, Gomel, Belarus
  • 5Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, North Cyprus
  • 6School of Life Sciences, University of Sussex, Brighton, UK

Abstract

Purpose
Although the conventional gamma ray brachytherapy has been successful in treating endometrioid endometrial adenocarcinoma (EC), the molecular and cellular mechanisms of this anti-tumorigenic response remain unclear. Therefore, we investigated whether gamma ray irradiation induces changes in the number of FoxP3+ T-regulatory lymphocytes (Tregs), CD56+ natural killer cells (NK), and the expression of progesterone receptor membrane component 1 (PGRMC1) in the tumor microenvironment (TME).
Materials and Methods
According to the inclusion criteria, 127 cases were selected and grouped into irradiation-treated (Rad+) and control (underwent surgery) groups and analyzed using immunohistochemistry. Predictive prognostic values were analyzed using Mann-Whitney U test, ROC analysis, relative risk, log-rank, Spearman rank tests and multivariate Cox’s regression.
Results
We observed significant differences (p < 0.001) between the radiation-treated patients and the control groups in FoxP3+ Tregs numbers, CD56+ NK cells and PGRMC1 expression. Gamma ray induced a 3.71- and 3.39-fold increase in the infiltration of FoxP3+ cells, CD56+ NK cells, respectively and 0.0034-fold change in PGRMC1 expression. Univariate and multivariate analyses revealed predictive role of the parameters. In the irradiated patients’ group, inverted correlations between clinical unfavorable outcome, FoxP3+ Tregs and CD56+ NK cells were observed.
Conclusion
Our results suggest an immune-modulating role, specifically by increasing immune cell infiltration, of gamma radiation in the TME which may potentially be utilized as biomarkers in prognostic values.

Keyword

Gamma rays; CD56; FoxP3; PGRMC1; Tumor microenvironment; Endometrioid endometrial carcinoma
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