Proximity and metabolic activity of the Tumour Microenvironment as predictors of survival in High Grade Serous Ovarian Cancer (HGSOC)

High grade serous ovarian cancer (HGSOC) is a lethal gynaecological malignancy, most often detected at the late stages of disease, and at which point, response to therapy is only seen in a minority of patients. As new treatments are introduced, there is a growing need to better understand how the tumour microenvironment (TME) is predictive of therapeutic benefit. Here, we spatially analysed tumour samples from 55 HGSOC patients using high-plex spatial proteomics to characterise the TME and define the contributions to patient survival in cisplatin resistance. Using a custom-developed 48-plex cyclic immunofluorescent protein panel, we analysed tumour and immune cell interactions and their functional and metabolic profiles. We found that a higher number of CD66+ cells in a 50µm radius of tumour cells (p = 0.025) and a higher number of cytotoxic CD8 T -Cells within a 10 µm radius of the tumour boundary were associated with improved overall survival (p = 0.03). We found that in areas of metabolically active tumour cells, the proximity of T-Reg Cells was associated with better overall survival when the activity of the tumour was increased in either citrate synthase activity (p = 0.0064) or high nitric oxide (p = 0.017). However, with metabolically less active tumours, there was an association with worse overall survival (p = 0.033). Taken together, our data suggest that a comprehensive functional understanding of the TME is needed to quantify the therapeutic benefits of immunotherapy in HGSOC.