Mouse ovarian cancer models recapitulate the human tumor microenvironment and patient response to treatment

Although there are many prospective targets in the tumor microenvironment (TME) of high-grade serous ovarian cancer (HGSOC), pre-clinical testing is challenging especially as there is limited information on the murine TME. Here, we have characterized the TME of six orthotopic, transplantable syngeneic HGSOC lines established from genetic models and compared these to patient biopsies. This analysis identified significant correlations between the transcriptome, host cell infiltrates, immune response, matrisome, vasculature and tissue modulus of mouse and human TMEs, with several stromal and malignant cell targets in common. However, each model showed distinct differences and potential vulnerabilities that enabled us to predict response to chemotherapy and an anti-IL-6 antibody. The transcriptional profiles of the mouse tumors that differed in chemotherapy response were able to classify chemotherapy-sensitive and -refractory patient tumors. These models provide useful pre-clinical tools and may help identify subgroups of HGSOC patients most likely to respond to specific therapies. Overall design: RNA sequencing on whole tumours from: A) six transplantable syngeneic murine HGSOC lines (HGS1, n =3 ; HGS2, n=4; HGS3, n = 4; HGS4, n=5 ; 60577, n=5; 30200, n =4) along with tumours from a genetically modified mouse model (n = 3) and control non-diseased omental tissue (C57Bl/6, n=5 ; FVB, n=4) and B) human HGSOC omental metastasis tumours (n=5) and uninvolved omenta (n=3).