Zinovkin Dmitry Aleksandrovich, Lyzikova Yulia Anatolievna, Nadyrov Eldar Arkadievich, Petrenyov Daniil Rudolfovich, Yuzugulen Jale, Pranjol Md Zahidul Islam
Department of Pathology, Gomel State Medical University, Gomel, Belarus.
Department of Obstetrics and Gynecology, Gomel State Medical University, Gomel, Belarus.
Radiat Oncol J. 2021 Dec;39(4):324-333. doi: 10.3857/roj.2021.00472. Epub 2021 Aug 17.
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).
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.
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.
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.
尽管传统的伽马射线近距离放射治疗已成功用于治疗子宫内膜样腺癌（EC），但这种抗肿瘤反应的分子和细胞机制仍不清楚。因此，我们研究了伽马射线照射是否会诱导肿瘤微环境（TME）中FoxP3 +调节性T淋巴细胞（Tregs）、CD56 +自然杀伤细胞（NK）数量的变化以及孕激素受体膜成分1（PGRMC1）的表达。
根据纳入标准，选择127例患者，分为放疗组（Rad +）和对照组（接受手术），并采用免疫组织化学进行分析。使用Mann-Whitney U检验、ROC分析、相对风险、对数秩检验、Spearman秩检验和多变量Cox回归分析预测预后价值。
我们观察到放疗患者与对照组在FoxP3 + Tregs数量、CD56 + NK细胞和PGRMC1表达方面存在显著差异（p < 0.001）。伽马射线分别使FoxP3 +细胞、CD56 + NK细胞的浸润增加了3.71倍和3.39倍，PGRMC1表达变化了0.0034倍。单变量和多变量分析揭示了这些参数的预测作用。在接受照射的患者组中，观察到临床不良结局与FoxP3 + Tregs和CD56 + NK细胞之间呈负相关。
我们的结果表明，伽马射线在TME中具有免疫调节作用，特别是通过增加免疫细胞浸润，这可能潜在地用作预后价值的生物标志物。
