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休眠转移灶表现出一种独特的表型,主要由 Ch25h 基因促进,并由 T 淋巴细胞维持其休眠状态

英文原题:Dormant Metastases Exhibit a Unique Phenotype Primarily Promoted by the Ch25h Gene and Are Maintained in Dormancy by T Lymphocytes.

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Dormant Metastases Exhibit a Unique Phenotype Primarily Promoted by the Ch25h Gene and Are Maintained in Dormancy by T Lymphocytes.

PubMed 2025/10/26(内容时间) MedComm (2020) Q1 · IF 14.1(JCR 2025)

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中文摘要

在癌症发展过程中,转移细胞常进入一种可被免疫系统控制的休眠状态。我们实验室建立了一种转移性免疫休眠的临床前小鼠模型。野生型小鼠的免疫系统可控制自发性休眠转移灶。宿主免疫系统的耗竭会导致这些转移灶苏醒并进展。

我们将休眠转移灶与裸鼠转移灶以及从未进入休眠状态的显性转移灶进行比较。研究结果表明,休眠转移灶表现出独特且分化的表型。其在体外对营养限制条件、化疗药物和细胞因子的不同反应证明了这一点。

此外,休眠转移灶表现出独特的基因表达转录模式,该模式主要由 Ch25h 基因驱动。另外,分析还揭示了 microRNA 的差异表达,其中 mir-142-3p 水平升高并呈从头表达。休眠转移灶的微环境中 T 淋巴细胞(细胞毒性 T 淋巴细胞、辅助性 T 淋巴细胞和 γδ T 细胞)及中性粒细胞增多。受免疫控制的休眠转移灶表现出独特表型,可用于发现新的生物标志物,以及开发清除这些转移灶或控制显性转移灶的疗法。

展开英文摘要原文

During the course of cancer, metastatic cells frequently enter a state of dormancy that can be controlled by the immune system. In our laboratory, we developed a preclinical mouse model of metastatic immunodormancy. Dormant spontaneous metastases are controlled by the immune system of wild-type mice. Depletion of the host immune system causes these metastases to awaken and progress.

Dormant metastases are compared with nude metastases and overt metastases that have never been in dormancy. The findings of the study indicate that the dormant metastases exhibit a unique and differentiated phenotype. This is evidenced by their varied response to nutrient-restrictive conditions, chemotherapeutic agents, and cytokines in vitro.

Furthermore, dormant metastases exhibit a distinctive transcriptional pattern of gene expression, which is predominantly promoted by the Ch25h gene.

Additionally, the analysis revealed differential expression of microRNAs, with elevated levels of mir-142-3p being expressed de novo. The microenvironment of dormant metastases shows an increase in T lymphocytes (cytotoxic and helper T lymphocytes and γδ T cells) and neutrophils. Immune-controlled dormant metastases exhibit a unique phenotype that can be exploited to discover new biomarkers, as well as to develop therapies to eradicate them or control overt metastases.

论文信息

作者
Chamorro V、Algarra I、Sanz V、Pulido M、Romero I、Chico E、Millán M、Escaño-Maestre M
单位
Servicio De Análisis Clínicos e Inmunología UGC Laboratorio Clínico Hospital Universitario Virgen De Las Nieves Granada Spain.Spain
期刊
MedComm2025 Nov
原文标识
PubMed 41159143 · DOI 10.1002/mco2.70437