Komar Zofia M, Bavelaar Mieke, Kageler Ellen, Verkaik Nicole S, van Rosmalen Mandy M, van Deurzen Carolien H M, den Bakker Michael A, Kanaar Roland, Houtsmuller Adriaan B, van den Bosch Thierry P P, Jager Agnes, van Gent Dik C
Department of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Neoplasia. 2025 Oct;68:101221. doi: 10.1016/j.neo.2025.101221. Epub 2025 Aug 21.
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.
乳腺癌的个性化医疗需要预测性生物标志物,以便为每个患者选择最佳治疗方案。化疗或免疫治疗反应的个性化尤其具有挑战性,因为分子标志物似乎对治疗反应的预测性不足。用于治疗选择的功能测定可能是解决这一困境的方法。一种有趣的方法是对精确切割的肿瘤切片进行体外培养,例如我们之前描述的基于运动的组织体外(MOTEX)方法。这种培养方法的优点是它包含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培养中可维持数天,且活力无明显丧失。即使使用微管毒物紫杉醇进行处理,也不会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会影响免疫细胞组成,这与其细胞毒性特性相符。因此,我们得出结论,乳腺癌组织切片的MOTEX培养可用于研究涉及免疫系统的治疗效果。这为开发免疫检查点抑制剂治疗及其他需要检测系统中免疫成分的治疗干预的预测性测定开辟了前景。