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子宫内膜癌患者 TIL(肿瘤浸润淋巴细胞)中雌激素受体 α 的表达

英文原题:Estrogen receptor α expression in tumor-infiltrating lymphocytes from patients with endometrial cancer.

查看英文原题

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

PubMed 2025/12/19(内容时间) Oncol Lett Q3 · IF 2.1(JCR 2025)

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中文摘要

子宫内膜癌(EC)中,肿瘤微环境(包括激素环境)与免疫系统的复杂交互对肿瘤生长具有重要作用。雌二醇介导的雌激素受体(ER)信号对宫颈癌患者调节性TIL(肿瘤浸润淋巴细胞)的功能至关重要。

因此,本研究检测了EC组织浸润淋巴细胞中的ER相对水平,并考察其表达差异是否与临床病理特征(包括分子分型)相关。研究收集82例确诊EC患者的肿瘤和正常子宫内膜样本,其中54份样本经评估足够且符合后续研究要求。采用流式细胞术检测辅助性T淋巴细胞(Th)、细胞毒性T淋巴细胞(CTL)和B淋巴细胞(B细胞)的频率,以及各细胞中ER阳性比例;进一步通过中位荧光强度(MFI)评估这些TIL亚群中ER的绝对水平,并分析其与包括分子亚型在内的临床病理特征之间的关联。所有研究的TIL亚群中,ER水平均显著低于正常子宫内膜对照组织。

然而,与对照相比,EC中Th细胞及ER阳性Th细胞频率显著增加,而CTL及ER阳性CTL频率显著降低。高级别EC肿瘤及错配修复缺陷肿瘤中,ER阳性B细胞频率显著升高。通过MFI测得的TIL亚群ER表达与患者体重指数呈负相关,但与其他所考察的临床病理预后因素无相关性。TIL中ER降低的机制、其预后意义和潜在治疗靶向价值仍需进一步研究,包括分子背景探究和功能验证实验。

展开英文摘要原文

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 (ER ) signaling is critical for the function of regulatory tumor-infiltrating lymphocytes (TILs) in patients with cervical cancer.

Therefore, the present study investigated the relative ER 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 ER were examined using flow cytometry.

Furthermore, the expression of ER in these TIL subpopulations was evaluated using median fluorescence intensity (MFI) to assess the absolute level of ER in the studied lymphocytes. Associations of ER levels in TILs with clinicopathological characteristics, including molecular subtypes, were measured. All the studied TIL subpopulations showed a significantly lower ER level compared with normal endometrial tissue, which constituted the control group.

However, the frequencies of Th cells and Th cells expressing ER were significantly increased, while the frequencies of CTLs and CTLs expressing ER were significantly decreased in EC compared with the control. The frequency of B cells expressing ER was significantly increased in high grade EC tumors and tumors harboring mismatch repair deficiency.

ER 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 ER 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.

论文信息

作者
Jedryka MA、Slawek A、Kubik P、Lorek D、Kedzierska AE、Czekanski A、Matkowski R、Chelmonska-Soyta A
第一作者单位
Department of Oncology, Wroclaw Medical University, 53-413 Wroclaw, Poland.Poland
通讯作者单位
Laboratory of Reproductive Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.Poland
期刊
Oncology letters2026 Feb
原文标识
PubMed 41476451 · DOI 10.3892/ol.2025.15436