Developing ex-vivo 3D mammary tumor/organoid culture system for evaluating interactive immune check point molecular and cellular activities in tumor stromal microenvironment

To improve and optimize a multi-factorial, ex-vivo, 3D-culture/co-cultivation system (see diagram below and in Preliminary Studies) for studying the interactions among different and defined cell types of mammary tumor microenvironments. To characterize and investigate, using the optimized ex-vivo 3D culture system, the possible or candidate “immune check point” effect of three phytochemicals, including shikonin, BP-E-F1 and Q2-3, on the interactions between mammary tumor cells and tumor-associated fibroblasts. To evaluate specific molecular and cellular activities for the interactions between tumor cells and key innate immune cells (including MDSCs, macrophages and DCs), in response to the three selected anti-inflammatory phytomedicines. To evaluate, using RNA Seq and proteome profiling, other possible driver or master factors that may also play a key role in the phytochemical-mediated anti-metastasis response.