The central hypothesis of our project is that a single-cell characterization of cancer cell-tumor microenvironment interactions will elucidate novel targets to activate the immune landscape of high-grade serous ovarian cancer tumors. High-grade serous ovarian cancer is associated with a high fatality rate. Overcoming the challenges to develop more effective therapeutic approaches lies in advancing our understanding of the factors in the cancer cells and the surrounding tumor microenvironment that limit responses to current therapies. There are several factors of high-grade serous ovarian tumors that can impair the infiltration, presence, or activity of tumorinfiltrating lymphocytes, creating an immune escape landscape. Therefore, we need a deeper understanding of the immune landscape of high-grade serous OvCa tumors to discover drugs that effectively activate an anticancer immune microenvironment in these tumors.

Aim 2: Develop an accurate, predictive model to evaluate immune response in human high-grade serous ovarian cancer tumors

Goal: Incorporate the immune landscape into our 3D organotypic model of the tumor microenvironment of high-grade serous ovarian cancer.

We established methods for cultivating and characterizing OvCa cells and CAFs, the principal cell types in OvCa tumors. Additionally, we have established methods for the isolation of NK and T cells from peripheral blood and the corresponding ovarian and omental tumors. A 3D model using human primary cells is our best in vitro approximation of in vivo cell-cell dynamics and can be utilized to study solid tumors. We will isolate immune cells from omental tumors of patients for our 3D culture to understand how they affect metastasis and therapy responses. Depending on our results, we will further explore other hallmarks of metastasis and chemo-resistance, including EMT, apoptosis, multi-drug resistance (MDR), and the cell cycle.

Primary cell isolation and culturing. Three-dimensional modeling of the tumor microenvironment. Viability assays. Fluorescent microscopy.

all software will be provided by the laboratory microsoft suite, prism, image J

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