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肾细胞癌中的 Eomesodermin:驱动肿瘤进展的表观遗传与免疫串扰(综述)

英文原题:Eomesodermin in renal cell carcinoma: Epigenetic and immune crosstalk driving tumor progression (Review).

PubMed 2026/09/18(内容时间) Int J Oncol Q1 · IF 7.3(JCR 2025)

研究概要

肾细胞癌(RCC)是肾癌的主要病理类型,约占所有肾癌病例的85%~95%。

中文摘要

肾细胞癌(RCC)是肾癌的主要病理类型,约占所有肾癌病例的85‑95%。尽管靶向治疗和免疫治疗已经出现,但耐药的发生仍然常见。Eomesodermin(Eomes)是T‑box转录因子家族的成员,将发育生物学和免疫调节与肿瘤相关程序联系起来。在RCC中,其功能似乎具有背景依赖性。在肿瘤浸润白细胞中,Eomes已被证明支持成熟NK 细胞和记忆CD8 + T细胞功能,而持续或失调的Eomes则与耗竭的CD8 + T细胞和Eomes阳性1型调节性T样免疫抑制细胞相关。在RCC肿瘤细胞本身以及基质/内皮区室中,目前的认识仍相对有限,现有证据往往来自间接的RCC通路研究、其他肿瘤类型或发育模型。本综述通过区分浸润白细胞、肿瘤细胞和基质/内皮区室,并通过区分直接RCC证据与间接推导的机制性推断,总结了RCC中Eomes相关机制。还根据现有证据的强度讨论了表观遗传调控、PI3K/Akt/mTOR信号传导、Wnt/β‑catenin信号传导、血管生成和治疗耐药。当前数据支持Eomes是一个探索性生物标志物和产生假说的治疗节点,而非已确立的临床靶点。然而,仍需进一步研究,以在RCC组织、单细胞和空间数据集中,以及实验性RCC模型中验证Eomes的细胞类型特异性功能。

展开英文摘要原文

Renal cell carcinoma (RCC) is the main pathological type of kidney cancer, which accounts for approximately 85‑95% of all cases of kidney cancer. Despite the emergence of targeted therapies and immunotherapies, however, the development of resistance remains common. Eomesodermin (Eomes) is a member of the T‑box transcription factor family that links both developmental biology and immune regulation with tumor‑associated programs. In RCC, its function appears to be context‑dependent. In tumor‑infiltrating leukocytes, Eomes has been shown to support mature natural killer cell and memory CD8 + T‑cell function, whereas persistent or dysregulated Eomes is associated with exhausted CD8 + T cells and Eomes‑positive type 1 regulatory T‑like immunosuppressive cells. In both intrinsic RCC tumor cells and stromal/endothelial compartments, current knowledge remains relatively limited, and what evidence there is has often been derived from indirect RCC pathway research, other tumor types or developmental models. The present review summarizes Eomes‑associated mechanisms in RCC through distinguishing among infiltrating leukocytes, tumor cells and stromal/endothelial compartments, and also through separating direct RCC evidence from indirectly derived mechanistic inferences. Epigenetic regulation, PI3K/Akt/mTOR signaling, Wnt/β‑catenin signaling, angiogenesis and therapeutic resistance are also discussed according to the strength of the available evidence. Current data support that Eomes stands as an exploratory biomarker and hypothesis‑generating therapeutic node, rather than as an established clinical target. Further research should be performed, however, to validate the cell‑type‑specific functions of Eomes in RCC tissues, single‑cell and spatial datasets, in addition to experimental RCC models.

论文信息

作者
Che Z、Huang D、Lin J、Wang X、Feng R、Che X、Wang Y
单位
Key Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education, Department of Urology, The First Affiliated Hospital, Hainan Medical University, Haikou, Hainan 570102, P.R. China.China
文献类型
综述
期刊
International journal of oncology2026 Nov
原文标识
PubMed 42757465 · DOI 10.3892/ijo.2026.5941