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肿瘤浸润调节性T细胞与患有恶性肿瘤犬不良预后的关联

Association of tumour-infiltrating regulatory T cells with adverse outcomes in dogs with malignant tumours.

作者信息

Sakai K, Maeda S, Yamada Y, Chambers J K, Uchida K, Nakayama H, Yonezawa T, Matsuki N

机构信息

Department of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

出版信息

Vet Comp Oncol. 2018 Sep;16(3):330-336. doi: 10.1111/vco.12383. Epub 2018 Jan 11.

DOI:10.1111/vco.12383
PMID:29322606
Abstract

Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and associate with poor prognosis in humans. However, data on association of Treg infiltration with prognosis is limited in canine tumours. The purpose of this study was to examine the number of tumour-infiltrating Tregs and its association with overall survival (OS) in dogs with malignant tumours. The following 168 canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number of forkhead box P3 (Foxp3)-positive Tregs in intratumoral and peritumoral areas was investigated by immunohistochemistry. OS was compared between high and low Treg groups. The number of intratumoral and peritumoral Foxp3-positive Tregs was significantly higher in OMM, OSCC, PA and MC compared with each normal tissue. There were few Foxp3-positive Tregs in MCT and HCC. With intratumoral Tregs, the OS in the high Treg group was significantly shorter than that in the low Treg group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant difference for OS between the 2 groups in each tumour type. These results suggest that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs are associated with poor prognosis in some solid tumour types.

摘要

调节性T细胞(Tregs)浸润多种肿瘤组织,且与人类预后不良相关。然而,在犬类肿瘤中,关于Treg浸润与预后关系的数据有限。本研究的目的是检测恶性肿瘤犬的肿瘤浸润Tregs数量及其与总生存期(OS)的关系。纳入了以下168例犬类肿瘤:37例口腔恶性黑色素瘤(OMM);14例口腔鳞状细胞癌(OSCC);16例肺腺癌(PA);37例乳腺癌(MC);36例肥大细胞瘤(MCT)和28例肝细胞癌(HCC)。从8只健康犬获取正常组织作为对照。通过免疫组织化学研究肿瘤内和肿瘤周围区域中叉头框P3(Foxp3)阳性Tregs的数量。比较高Treg组和低Treg组的OS。与各正常组织相比,OMM、OSCC、PA和MC中肿瘤内和肿瘤周围的Foxp3阳性Tregs数量显著更高。MCT和HCC中Foxp3阳性Tregs很少。对于肿瘤内Tregs,在OMM、OSCC和PA中,高Treg组的OS显著短于低Treg组。对于肿瘤周围Tregs,各肿瘤类型的两组之间OS无显著差异。这些结果表明,Tregs浸润多种犬类肿瘤,且在某些实体瘤类型中Tregs的丰度与预后不良相关。

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