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

Abstract

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.

Zusammenfassung

Das hochgradige seröse Tubo-Ovarialkarzinom ist die häufigste und aggressivste Art des Ovarialkarzinoms. Gekennzeichnet ist diese Tumorart durch genomische Instabilität sowie eine ausgeprägte Tumorheterogenität zwischen verschiedenen Patientinnen und verschiedenen Tumorlokalisationen innerhalb einer Patientin. In unterschiedlichen Tumorlokalisationen beeinflussen spezifische Signalwege zwischen Krebszellen und dem Tumormikromilieu verschiedene Tumorekosysteme, die sich auf das Therapieansprechen und die Krankheitsprogression auswirken. Krebszellenspezifische genomische Defekte tragen zusätzlich zur Diversität der Tumor-Immunantwort bei. Eine homologe Rekombinationsdefizienz gilt in 50% der Fälle als wichtiger onkogener Faktor für unterschiedliche Mechanismen der Tumorevolution. Der heterogene Charakter dieser Tumormikromilieus stellt eine große Herausforderung dar bei der Identifizierung von prädiktiven Biomarkern für das Therapieansprechen und bei der Stratifikation von Untergruppen, die auf eine Immuntherapie ansprechen.

Keywords

high-grade serous ovarian cancer - genomic instability - immune response - tumor heterogeneity

Schlüsselwörter

hochgradiges seröses Ovarialkarzinom - genomische Instabilität - Immunreaktion - Tumorheterogenität

Publication History

Received: 11 January 2025

Accepted after revision: 11 May 2025

Article published online:
11 June 2025

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