Abstract 4551: Reconstructing the metastatic tumor microenvironment of high grade serous ovarian cancer: understanding the contribution of malignant cells

Abstract

Abstract Following a ‘deconstruction’ of the metastatic tumor microenvironment (TME) of high grade serous ovarian cancer (HGSOC), we developed 3-dimensional (3D) human multicellular in vitro models using patient-derived primary cells and HGSOC malignant cell lines. In this study, we used these 3D in vitro human models to study how malignant cells influence the surrounding TME. Using patient-derived primary adipocytes, fibroblasts and mesothelial cells isolated from macroscopically normal omentum (the primary site of metastasis in HGSOC) from women undergoing gynaeco-oncology surgery, we built multicellular models combining those cells with different high grade serous malignant cell lines and monocytes isolated from healthy individuals. We found that peripheral blood monocytes were able to differentiate and polarize to macrophages in our pentacultures (i.e., five different cell types) with phenotypes also found in HGSOC omental metastases. In addition, the cells in our pentaculture models self-rearranged in ways that were dependent on the HGSOC malignant cell lines used in the culture. Macrophage phenotype and cytokine secretion from the multicellular cultures was also influenced by the different malignant HGSOC cell lines used in the model. RNAseq analysis of the pentacultures showed that the cultures clustered according to the malignant cell line used. In addition, we were able to identify some gene expression clusters in the macrophages and fibroblasts of the pentacultures that matched those found by single cell RNAseq analysis of human HGSOC biopsies. These human 3D in vitro multicellular models allow us to define the contribution of each cell type to tumor growth and spread, and also provide us a semi-high throughput platform to investigate antibody or drug targets. Citation Format: Beatrice Malacrida, Samar Elorbany, Eleni Maniati, Florian Laforets, Ranjit Manchanda, Frances R. Balkwill. Reconstructing the metastatic tumor microenvironment of high grade serous ovarian cancer: understanding the contribution of malignant cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4551.