The limited success of immune checkpoint inhibitors (ICIs) in high-grade serous ovarian carcinoma (HGSOC) highlights the need to better understand the immunosuppressive microenvironment of ovarian cancer. This project aims at characterizing the immunoevasion mechanisms that are employed by ovarian cancer cells. As most HGSOC patients receive chemotherapy (CT) as first-line therapy, we also want to investigate the tumor microenvironment's (TME) evolution during CT and its effects on immune responses and tumor immune evasion. Through a comparative analysis of the TME before and after CT, we will identify more effective personalized ICI-CT combination.

We analyzed tumors from 145 HGSOC patients untreated or treated by chemotherapy. Cyclic immunofluorescence (Cyc-IF), a spatially oriented single-cell proteomic approach, was used to measure the expression of 80 proteins and the Nanostring GeoMX platform was used to measure expression of over 4,000 genes in each sample.

Our analysis suggested distinct gene and protein expression profiles in the tumor and stromal compartments of untreated and treated tumors. Amongst those changes, we have observed a remodeling of the extracellular matrix in the stroma, potentially impacting immune cell infiltration. Moreover, we identified numerous genes associated with ribosomal changes and observed modifications in pathways related to both innate and adaptive immunity. The ratio of M2 to M1 macrophages was lower in samples from patients who received neoadjuvant chemotherapy. Interestingly, certain patients who received neoadjuvant chemotherapy exhibited higher B7H4 expression on cancer cells, while PD-L1 expression showed no significant differences. This highlights a promising avenue for personalized immunotherapies in ovarian cancer.

In conclusion, this comprehensive analysis of ovarian TME represents a step towards personalized therapies that will increase the likelihood of effective anti-tumor immune responses and decrease disease recurrence risk.