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Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance

机译：成像肿瘤间质相互作用的化学疗法揭示了微环境对耐药性的贡献。

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Little is known about the dynamics of cancer cell death in response to therapy in the tumor microenvironment. Intravital microscopy of chemotherapy-treated mouse mammary carcinomas allowed us to follow drug distribution, cell death, and tumor-stroma interactions. We observed associations between vascular leakage and response to doxorubicin, including improved response in matrix metalloproteinase-9 null mice that had increased vascular leakage. Furthermore, we observed CCR2-dependent infiltration of myeloid cells after treatment and that Ccr2 null host mice responded better to treatment with doxorubicin or cisplatin. These data show that the microenvironment contributes critically to drug response via regulation of vascular permeability and innate immune cell infiltration. Thus, live imaging can be used to gain insights into drug responses in situ.
机译：关于在肿瘤微环境中响应治疗的癌细胞死亡的动力学知之甚少。活体显微镜下化学疗法治疗的小鼠乳腺癌使我们能够追踪药物分布，细胞死亡和肿瘤-基质相互作用。我们观察到血管渗漏与对阿霉素的反应之间的关联，包括在血管渗漏增加的基质金属蛋白酶9无效小鼠中改善的反应。此外，我们观察到治疗后骨髓细胞的CCR2依赖性浸润，而Ccr2无效宿主小鼠对阿霉素或顺铂治疗的反应更好。这些数据表明，微环境通过调节血管渗透性和先天免疫细胞浸润，对药物反应起关键作用。因此，实时成像可用于就地了解药物反应。

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