A study recently published in Science Advances and supported in part by Ovarian Cancer Research Alliance has advanced scientists’ understanding of how to potentially overcome immune evasion in ovarian cancer.

The research team involved current and former Memorial Sloan Kettering Cancer Center researchers, including OCRA grantee Melica Brodeur MD, MSc, now at McGill University, who led the study. She co-authored the study with OCRA grantee and senior author Dmitriy Zamarin, MD, PhD, now at Icahn School of Medicine at Mount Sinai, and senior author Britta Weigelt, PhD, at Memorial Sloan Kettering Cancer Center. The team’s findings reveal a likely connection between mutations in a specific gene and the immune system’s response to ovarian cancer.
The scientists demonstrated that loss-of-function mutations in a gene known as SMARCA4 are associated with an enhanced immune response in ovarian cancer tumors. The team used genetically engineered mouse models to evaluate how the loss of SMARCA4 impacts the tumor microenvironment and discovered that it improved infiltration and activation of immune cells as well as delayed tumor growth. They then replicated this response by targeting the protein encoded by SMARCA4, BRG1, with an inhibitor. Their learnings suggest that SMARCA4 mutation has potential as a predictor of immunotherapy response and that SMARCA4/BRG1 may serve as a therapeutic target to improve the efficacy of immunotherapy in ovarian cancer.
Visit Science Advances to read the full study, which was partially funded by OCRA’s 2022 Mentored Investigator Grant awarded to Dr. Brodeur.
Dr. Brodeur’s grant was made possible in part by a generous donation from The Wasily Family Foundation.