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基于运动的离体(MOTEX)培养乳腺肿瘤切片维持微环境组成

英文原题:Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition.

查看英文原题

Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition.

PubMed 2025/08/21(内容时间) Neoplasia Q2 · IF 4.8(JCR 2025)

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中文摘要

乳腺癌(BrC)的个性化医疗需要预测性生物标志物,以为每位个体患者选择最佳治疗选项。化疗或免疫治疗反应的个性化尤为具有挑战性,因为分子标志物似乎对治疗反应的预测能力不足。用于治疗选择的功能性检测可能是解决这一困境的方法。一种有趣的方法是精确切割肿瘤切片的离体培养,例如我们之前描述的基于运动的组织离体(MOTEX)方法。这种培养方法的优势在于它保留了肿瘤中的所有细胞类型,包括各种免疫细胞群体。

我们在此表明,巨噬细胞、B细胞和T细胞群体在MOTEX培养中维持数天而无明显的活力丧失。即使使用微管毒物紫杉醇处理,也未显著降低免疫细胞丰度或活力。

然而,基于蒽环类药物的化疗确实影响了免疫细胞组成,正如基于其细胞毒性特性所预期的那样。因此,我们得出结论,BrC组织切片的MOTEX培养可用于研究涉及免疫系统的治疗的效果。这为开发免疫检查点抑制剂治疗以及其他需要在检测系统中包含免疫组分的治疗干预措施的预测性检测开辟了前景。

展开英文摘要原文

Personalized medicine for breast cancer (BrC) requires predictive biomarkers to select the optimal therapeutic option for each individual patient. Personalization of chemotherapy or immunotherapy responses is particularly challenging, as molecular markers do not appear to be sufficiently predictive for therapy response.

Functional assays for therapy selection may be the solution for this dilemma. An interesting approach is ex vivo cultures of precision cut tumor slices, such as the MOtion-based Tissue EX vivo (MOTEX) method that we described previously. This culture method has the advantage that it carries all cell types in the tumor, including various immune cell populations.

We here show, that macrophages, B-cells and T-cell populations are maintained in the MOTEX culture for several days without apparent loss of viability. Even treatment with the microtubule poison paclitaxel did not reduce immune cell abundance or viability significantly. Anthracycline-based chemotherapy, however, did affect immune cell composition, as expected based on its cytotoxic properties.

Therefore, we conclude that MOTEX culture of BrC tissue slices can be used to investigate effect of treatments that involve the immune system. This opens perspectives to develop predictive assays for immune checkpoint inhibitor treatment and other therapeutic interventions that require immune components in the assay system.

论文信息

作者
Komar ZM、Bavelaar M、Kageler E、Verkaik NS、van Rosmalen MM、van Deurzen CHM、den Bakker MA、Kanaar R
第一作者单位
Department of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.Netherlands
通讯作者单位
Department of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Oncode Institute, Erasmus MC, Rotterdam, The Netherlands. Electronic address: d.vangent@erasmusmc.nl.Netherlands
期刊
Neoplasia (New York, N.Y.)2025 Oct
原文标识
PubMed 40845489 · DOI 10.1016/j.neo.2025.101221