Seed Funding Program 2022
OVERCOM
Ovarian Cancer Tumor Microenvironment treated with PARPi and PD-L1i
Coordinators
Frederik Marmé
Gynaecological Clinic, UMM
Benedikt Brors
Applied Bioinformatics, DKFZ
Detailed description
Despite the efficacy observed with immunotherapy in other cancers, such as melanoma, low response rates and several negative phase III trials make ovarian cancer a challenging disease for immunotherapy. One approach to increase efficacy is to combine immune checkpoint inhibitors with other therapies like PARP inhibitors. PARP inhibitors have been shown to activate the innate immune system through activation of the cGAS/Sting pathway that lead to a T cell infiltrate in preclinical models.
The goal of this project is to understand changes in tumor-immune interaction in patients receiving PARP inhibitor and immune checkpoint inhibitor treatment.
This project will have use tissue samples from previously untreated patients with high-grade ovarian carcinomas receiving a PARP inhibitor alone or in combination with an immune checkpoint inhibitor as part of an investigator-initiated study. Samples will be obtained prior to the initiation of treatment and after 4 weeks of therapy. Plasma will be collected for ctDNA analysis in parallel. It is planned to analyze liquid biopsies as well as primary tumor tissue using multiple omics-techniques such as single cell and spatial transcriptomics as well characterization of primary organoid cultures. By elucidating changes in the cellular transcriptional architecture and changes in ctDNA, factors that drive resistance and therapeutic outcome will be predicted.