Mencattini Arianna, De Ninno Adele, Mancini Jacopo, Businaro Luca, Martinelli Eugenio, Schiavoni Giovanna, Mattei Fabrizio
Department of Electronic Engineering, University of Rome Tor Vergata, Rome, Italy.
Institute for Photonics and Nanotechnology, Italian National Research Council, Rome, Italy; Department of Civil Engineering and Computer Science, University of Rome Tor Vergata, Rome, Italy.
Methods Enzymol. 2020;632:479-502. doi: 10.1016/bs.mie.2019.06.012. Epub 2019 Jul 26.
Understanding the interactions between immune and cancer cells occurring within the tumor microenvironment is a prerequisite for successful and personalized anti-cancer therapies. Microfluidic devices, coupled to advanced microscopy systems and automated analytical tools, can represent an innovative approach for high-throughput investigations on immune cell-cancer interactions. In order to study such interactions and to evaluate how therapeutic agents can affect this crosstalk, we employed two ad hoc fabricated microfluidic platforms reproducing advanced 2D or 3D tumor immune microenvironments. In the first type of chip, we confronted the capacity of tumor cells embedded in Matrigel containing one drug or Matrigel containing a combination of two drugs to attract differentially immune cells, by fluorescence microscopy analyses. In the second chip, we investigated the migratory/interaction response of naïve immune cells to danger signals emanated from tumor cells treated with an immunogenic drug, by time-lapse microscopy and automated tracking analysis. We demonstrate that microfluidic platforms and their associated high-throughput computed analyses can represent versatile and smart systems to: (i) monitor and quantify the recruitment and interactions of the immune cells with cancer in a controlled environment, (ii) evaluate the immunogenic effects of anti-cancer therapeutic agents and (iii) evaluate the immunogenic efficacy of combinatorial regimens with respect to single agents.
了解肿瘤微环境中免疫细胞与癌细胞之间的相互作用是成功实施个性化抗癌治疗的前提条件。微流控装置与先进的显微镜系统及自动化分析工具相结合，可为免疫细胞与癌细胞相互作用的高通量研究提供一种创新方法。为了研究此类相互作用并评估治疗药物如何影响这种相互作用，我们采用了两个专门制造的微流控平台，它们能够重现先进的二维或三维肿瘤免疫微环境。在第一种芯片中，我们通过荧光显微镜分析，比较了包埋于含有一种药物的基质胶或含有两种药物组合的基质胶中的肿瘤细胞吸引不同免疫细胞的能力。在第二种芯片中，我们通过延时显微镜和自动跟踪分析，研究了未激活的免疫细胞对经免疫原性药物处理的肿瘤细胞发出的危险信号的迁移/相互作用反应。我们证明，微流控平台及其相关的高通量计算分析可代表多功能智能系统，用于：（i）在可控环境中监测和量化免疫细胞与癌细胞的募集及相互作用，（ii）评估抗癌治疗药物的免疫原性效应，以及（iii）评估联合用药方案相对于单一药物的免疫原性疗效。
