三阴性乳腺癌（TNBC）仍然难以治疗，特别是由于无效的免疫反应。目前的治疗主要针对细胞毒性作用，而（干）细胞疗法正在研究其免疫刺激能力以启动抗肿瘤免疫。在此，我们在基于 4T1 的 TNBC 导管内小鼠模型中测试了从马外周血中采集的马间充质干细胞 (eMSC) 作为创新异种免疫调节剂的彻底表征、同质且非致瘤性混合物。 eMSC 在全身注射后显着减少了 4T1 进展，单次剂量后就已经诱导原发性肿瘤中的炎症介质和 T 细胞流入。这些异种抗癌作用并不局限于 MSC，因为使用替代马上皮干细胞 (eEpSC) 进行的全身治疗模仿了报道的疾病减少效果。从机制上讲，有效的 eMSC 治疗并不依赖于脾脏作为全身包埋位点，而 CD4 和 CD8α T 细胞浸润和激活至关重要。这些结果表明，eMSC 以及可能的其他马干细胞类型可以成为进一步（前）临床评估的有价值的 TNBC 治疗策略。版权所有 © 2023 Steenbrugge、Pauwelyn、Demeyere、Devriendt、de Rooster、Sanders、Spaas 和 Meyer。

Triple-negative breast cancer (TNBC) remains difficult to treat, especially due to ineffective immune responses. Current treatments mainly aim at a cytotoxic effect, whereas (stem) cell therapies are being investigated for their immune stimulatory capacities to initiate the anti-tumor immunity. Here, a thoroughly characterized, homogenous and non-tumorigenic mixture of equine mesenchymal stem cells (eMSCs) harvested from horse peripheral blood as innovative xenogeneic immunomodulators were tested in a 4T1-based intraductal mouse model for TNBC. The eMSCs significantly reduced 4T1 progression upon systemic injection, with induction of inflammatory mediators and T-cell influx in primary tumors, already after a single dose. These xenogeneic anti-cancer effects were not restricted to MSCs as systemic treatment with alternative equine epithelial stem cells (eEpSCs) mimicked the reported disease reduction. Mechanistically, effective eMSC treatment did not rely on the spleen as systemic entrapment site, whereas CD4+ and CD8α+ T-cell infiltration and activation were critical. These results show that eMSCs and potentially also other equine stem cell types can be a valuable TNBC treatment strategy for further (pre)clinical evaluation.Copyright © 2023 Steenbrugge, Pauwelyn, Demeyere, Devriendt, de Rooster, Sanders, Spaas and Meyer.