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

• Zinovkin DA
• Lyzikova YA
• Nadyrov EA
• Petrenyov DR
• Yuzugulen J
• Pranjol MZI

• KMID: 2523735
• DOI: http://doi.org/10.3857/roj.2021.00472

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