Revisiting Genomic Instability, Tumor Microenvironment and Immune Response in High-Grade Serous Ovarian Cancer

High-grade serous tubo-ovarian cancer is the most common and aggressive type of ovarian cancer characterized by extensive genomic instability and marked inter- and intra-patient tumor heterogeneity. Tumor-site specific signaling crosstalk between cancer cells and the tumor microenvironment influences different tumor ecosystems that drive therapy response and disease progression. Cancer cell-intrinsic genomic aberrations further contribute to the diversity of the tumor immune landscape. Homologous recombination deficiency is considered a key oncogenic driver in 50% of the cases underlying distinctive mechanisms of tumor evolution. The heterogenous character of the tumor microenvironment represents a major challenge to identify predictive biomarkers of therapy response and to stratify subgroups amenable to immunotherapies.