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患有卵巢腺癌的蛋鸡中肿瘤特异性免疫和病理变化

英文原题:Tumor-specific immunological and pathological changes in layer chickens affected with ovarian adenocarcinoma.

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Tumor-specific immunological and pathological changes in layer chickens affected with ovarian adenocarcinoma.

PubMed 2026/08/06(内容时间) Dev Comp Immunol Q1 · IF 2.4(JCR 2025)

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中文摘要

人上皮性卵巢癌(EOC)的特征是深刻的免疫失调,其肿瘤微环境(TME)由免疫抑制性细胞群主导,如调节性T细胞,这些细胞主动限制抗肿瘤反应。老年蛋鸡(Gallus gallus domesticus)的自发性卵巢肿瘤与人类EOC的发生发展及组织病理学特征高度相似,使其成为研究人类EOC的理想模型。

在本研究中,我们检测了患有自发性卵巢肿瘤(OT)的母鸡卵巢TME中的病理学和免疫学变化。组织病理学特征与卵巢腺癌子宫内膜样亚型一致,而免疫组化分析显示与对照组相比,瘤内T细胞浸润减少。OT组织基因表达分析显示,与对照组相比,FoxP3、CD25、CD40、PD-1、LAG-3和GITR基因显著上调,同时IL-10转录增加,表明调节性T细胞扩增和效应T细胞耗竭。

此外,IL-1β、chTNFα和iNOS转录的显著降低提示细胞炎症激活受到抑制。这些发现表明,蛋鸡卵巢肿瘤经历了从炎症状态向免疫调节性、检查点主导的TME转变,这一观察与人类EOC相似。

本研究支持将蛋鸡作为研究人类卵巢癌及开发诊断和治疗策略的转化模型。

展开英文摘要原文

Human epithelial ovarian cancer (EOC) is characterized by profound immune dysregulation with a tumor microenvironment (TME) dominated by immunosuppressive populations such as regulatory T-cells that actively limit anti-tumor responses. Spontaneous ovarian tumors in older laying hens (Gallus gallus domesticus) closely resemble human EOC development and histopathological features, making them an ideal model to study human EOC.

Here, we examined pathological and immunological changes in ovarian TME from hens with spontaneous ovarian tumors (OT). Histopathological characterization was consistent with the endometrioid subtype of ovarian adenocarcinoma, while the immunohistochemistry analysis showed reduced intratumoral T cell infiltration compared to control.

The OT tissue gene expression analysis showed significant upregulation of FoxP3, CD25, CD40, PD-1, LAG-3 and GITR genes, accompanied by an increased IL-10 transcription compared to control, indicating regulatory T cell expansion and effector T cell exhaustion.

Furthermore, significant reduction in the IL-1β, chTNFα and iNOS transcription suggested suppressed cellular inflammatory activation.

These findings demonstrate that ovarian tumors in laying hens undergo a transition from an inflammatory state to an immunoregulatory, checkpoint-dominant TME, an observation resembling human EOC. This work supports the laying hen as a translational model for studying human ovarian cancer and developing diagnostic and therapeutic strategies.

论文信息

作者
Tyagi A、Chan PM、Stephens J、Crespo R、Rahe MC、Kulkarni RR
第一作者单位
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA.United States
通讯作者单位
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA. Electronic address: rrkulkar@ncsu.edu.United States
期刊
Developmental and comparative immunology2026 Sep
原文标识
PubMed 42562176 · DOI 10.1016/j.dci.2026.105703