Your Donations in Action: Jennifer Ma, MD

DNA repair deficiencies can drive genomic instability and alter the tumor microenvironment, potentially influencing immunotherapy effectiveness. However, these interactions are complex and not fully understood. Notably, prior studies have shown that patients with BRCA2-mutant tumors may experience better survival with immunotherapy than those with BRCA1 mutations.

For her 2022 RSNA Research Resident Grant, “Radiotherapeutic and Tumor Microenvironmental Determinations of Response to Immune Checkpoint Blockade in DNA Repair‐Deficient Breast Cancer,” Jennifer Ma, MD, assistant attending radiation oncologist in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center in New York, and colleagues examined how BRCA1 and BRCA2 mutations, despite affecting the same DNA repair pathway, lead to different immune behaviors in breast cancer.

Using mouse models, the researchers identified an innate immune signaling cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway that may influence tumor formation and immune-mediated tumor control.

The team found that when cGAS-STING was removed from BRCA2-deficient tumors, they were more likely to be spontaneously rejected by the immune system. This suggests that cGAS-STING signaling may play a context-dependent role in shaping antitumor immunity.

According to Dr. Ma, this work has informed new projects investigating how the cGAS-STING pathway influences tumor immunity in DNA repair-deficient cancers.

“In the longer term, these insights may inform biomarker-driven use of immunotherapy to guide more personalized treatment strategies across multiple cancer types,” Dr. Ma said.

Funding from the R&E Foundation was essential in helping Dr. Ma establish a clear and independent research direction within the rapidly evolving field of cancer immunogenomics.

“This experience was instrumental as I pursued full-time faculty positions, and it enabled me to generate the foundational data that will guide my research as I move forward in my career,” Dr. Ma said. “I am deeply grateful to the Foundation for its investment, which will continue to have a lasting impact as I advance my career as an academic radiation oncologist.”

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Read our previous Your Donations in Action story.