The overall goal is to uncover the immune regulatory cell types and their functional networks in order to develop and test effective combinations with immunotherapies and eventually improve the outcomes of patients with high-grade serous ovarian cancer (HGSOC).
The mechanisms of immune evasion in HGSOC are poorly understood. DNA damaging agents, such as platinum and Poly-ADP Ribose Polymerase (PARP) inhibitors, activate specific stimulatory, and also suppressive immune regulatory pathways in distinct molecular subtypes of HGSOCs. Lack of knowledge on the effects of conventional and novel DNA damaging agents on the immune microenvironment in different HGSOC molecular subtypes has led to a trial and error-based combining of DNA damaging- and immunotherapeutic agents. There now is a critical need for a deeper understanding of the dynamics of the immune regulatory cell types and pathways in HGSOC molecular subtypes to develop novel immunotherapeutic strategies and rational drug combinations for HGSOC.
We aim to discover the immune-cell subtypes, functional states, and pathways that contribute to immune regulation in HGSOC. Using a novel state-of-the-art multiplexed immunofluorescence technique (tCycIF) and advanced bioinformatic analyses, we aim to shed light into the critical immune-regulatory pathways in HGSOC molecular subtypes. We also use functional co-cultures of HGSOC cell lines and patient-derived organoids to assay the molecular mediators and spatial effectors of immune recognition before and after DNA damaging agents and immunotherapies.