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乳腺肿瘤基质成纤维细胞对体外免疫过程的影响。

Influence of the Breast Tumor Stromal Fibroblasts on Immunological Processes In Vitro.

作者信息

Saryglar R Yu, Lupatov A Yu, Vakhrushev I V, Karshieva S Sh, Bystrykh O A, Kuprin A V, Yarygin K N

机构信息

Institute of Biomedical Chemistry, Moscow, Russia.

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2025 Feb;178(4):552-559. doi: 10.1007/s10517-025-06372-4. Epub 2025 Mar 29.

Abstract

The effects of stromal cell cultures isolated from breast cancer tissue on the differentiation and maturation of dendritic cells and proliferation of lymphocytes were studied in vitro. The derived cultures had the fibroblast-like morphology and carried mesenchymal markers CD73 and CD90 in the absence of epithelial (CD326, CD24) and macrophage (CD68) markers. The cells also expressed CD44, CD10, and CD29 and had low levels of HLA-ABC expression. Intracellular expression of fibroblast activation protein (FAP), tenascin C, and α-SMA indicated their activated state and stromal origin. Analysis of the functional properties of the cells revealed their ability to suppress differentiation of dendritic cells from monocytes, as well as the proliferation of T lymphocytes. However, they had no significant effect on DC maturation. The results demonstrate that fibroblasts in the tumor stroma of breast cancer may have a suppressive effect on important mechanisms of the adaptive immunity and can be involved in the process of tumor escape from the immunological control.

摘要

研究了从乳腺癌组织中分离出的基质细胞培养物对树突状细胞分化和成熟以及淋巴细胞增殖的体外影响。所获得的培养物具有成纤维细胞样形态,在缺乏上皮(CD326、CD24)和巨噬细胞(CD68)标志物的情况下携带间充质标志物CD73和CD90。这些细胞还表达CD44、CD10和CD29,且HLA-ABC表达水平较低。成纤维细胞激活蛋白(FAP)、腱生蛋白C和α-平滑肌肌动蛋白的细胞内表达表明它们的激活状态和基质来源。对细胞功能特性的分析揭示了它们抑制单核细胞来源的树突状细胞分化以及T淋巴细胞增殖的能力。然而,它们对树突状细胞成熟没有显著影响。结果表明,乳腺癌肿瘤基质中的成纤维细胞可能对适应性免疫的重要机制具有抑制作用,并可能参与肿瘤逃避免疫控制的过程。

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