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乳腺癌相关脂肪组织中炎症变化的特征分析及其与未受影响的对侧乳房的比较。

Characterization of inflammatory changes in the breast cancer associated adipose tissue and comparison to the unaffected contralateral breast.

机构信息

Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.

The Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA; Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA.

出版信息

Surg Oncol. 2021 Dec;39:101659. doi: 10.1016/j.suronc.2021.101659. Epub 2021 Sep 9.

Abstract

BACKGROUND

Adipose tissue has emerged as an important window into cancer pathophysiology, revealing potential targets for novel therapeutic interventions. The goal of this study was to compare the breast adipose tissue (BrAT) immune milieu surrounding breast carcinoma and contralateral unaffected breast tissue obtained from the same patient.

MATERIALS AND METHODS

Patients undergoing bilateral mastectomy for unilateral breast cancer were enrolled for bilateral BrAT collection at the time of operation. After BrAT was processed, adipocyte and stromal vascular fraction (SVF) gene expression was quantified by PCR. SVF cells were also processed for flow cytometric immune cell characterization.

RESULTS

Twelve patients underwent bilateral mastectomy for unilateral ductal carcinoma. BrAT adipocyte CXCL2 gene expression trended higher in the tumor-affected breast as compared to the unaffected breast. Macrophage MCP-1 and PPARγ gene expression also tended to be higher in the tumor-affected breasts. T cell gene expression of FOXP3 (p = 0.0370) were significantly greater in tumor-affected breasts than unaffected breasts. Affected BrAT contained higher numbers of Th2 CD4 cells (p = 0.0165) and eosinophils (p = 0.0095) while trending towards increased macrophage and lower Th1 CD4 cells infiltration than tumor-affected BrAT.

CONCLUSION

This preliminary study aimed to identify the immunologic environment present within BrAT and is the first to directly compare this in individual patients' tumor-associated and unaffected BrAT. These findings suggest that cancer-affected BrAT had increased levels of T cell specific FOXP3 and higher levels of anti-inflammatory/regulatory cells compared to the contralateral BrAT.

摘要

背景

脂肪组织已成为癌症病理生理学的一个重要窗口,揭示了潜在的新治疗干预靶点。本研究的目的是比较乳腺癌患者双侧乳房脂肪组织(BrAT)和来自同一患者对侧未受影响的乳房组织的免疫微环境。

材料和方法

招募了因单侧乳腺癌而行双侧乳房切除术的患者,在手术时收集双侧 BrAT。处理 BrAT 后,通过 PCR 定量测定脂肪细胞和基质血管部分(SVF)的基因表达。还对 SVF 细胞进行流式细胞术免疫细胞特征分析。

结果

12 名患者因单侧导管癌而行双侧乳房切除术。与未受影响的乳房相比,肿瘤受累乳房的 BrAT 脂肪细胞 CXCL2 基因表达呈上升趋势。肿瘤受累乳房的巨噬细胞 MCP-1 和 PPARγ 基因表达也呈上升趋势。肿瘤受累乳房的 T 细胞 FOXP3 基因表达(p=0.0370)明显高于未受影响的乳房。受累 BrAT 含有更多的 Th2 CD4 细胞(p=0.0165)和嗜酸性粒细胞(p=0.0095),而浸润的巨噬细胞和 Th1 CD4 细胞则呈下降趋势。

结论

本初步研究旨在确定 BrAT 中存在的免疫学环境,并且是首次直接比较个体患者肿瘤相关和未受影响的 BrAT 中的这种环境。这些发现表明,与对侧 BrAT 相比,癌症受累 BrAT 中 T 细胞特异性 FOXP3 水平升高,抗炎/调节细胞水平升高。

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Immune microenvironment in different molecular subtypes of ductal breast carcinoma.不同分子亚型的乳腺导管癌中的免疫微环境。
Breast Cancer Res Treat. 2021 Jan;185(2):261-279. doi: 10.1007/s10549-020-05954-2. Epub 2020 Oct 3.
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The Interferon-Gamma Paradox in Cancer.癌症中的干扰素-γ 悖论。
J Interferon Cytokine Res. 2019 Jan;39(1):30-38. doi: 10.1089/jir.2018.0087. Epub 2018 Nov 9.

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