Modulating Chromatin Remodeling as a Strategy to Reverse Immune Evasion in Ovarian Cancer

Project summary

Ovarian cancer (OC) is the most lethal gynecological cancer. Immunotherapy, a treatment that helps the immune system fight cancer, has achieved remarkable responses in cancer types that were once fatal. Its successes have brought new hope to OC patients, however the latest OC clinical trials have shown overall disappointing responses with immune checkpoint blockade (ICB), the most common type of immunotherapy.

The interaction between OC and immune cells is influenced by various factors that alter the immune response and contribute to disease progression. Our research team is studying how to target these factors to improve the treatment of OC. One particular target is the SWI/SNF complex, made up of proteins involved in modifying the structure of DNA. In our recent study, we discovered that inhibiting the function of this complex increases the ability of OC cells to be recognized by the immune system. Another protein target, called HDAC6, that makes DNA less accessible has also been shown, when its function is inhibited, to increase the expression of immune-related genes.

Based on these findings, targeting both factors is a logical therapeutic strategy to sensitize OC to immunotherapy for a more effective response. Therefore, we propose in our study to combine HDAC6 and SWI/SNF inhibitors with ICB. This novel study may be used to overcome barriers to immunotherapy and help us reach our goal to improve outcomes for patients with OC.