Paola Betancur, PhD

Uncovering genomic modulators of immune suppression to enable more personalized treatments that activate the immune system to destroy cancer cells.

Impact

Breast cancer can activate an immune evasion program to effectively “hide” from the immune system. In this way, cancer cells avoid being detected as dangerous cells and continue to grow and expand. Despite our extensive knowledge about how cancer cells suppress the immune system, it is unclear whether these evasion mechanisms vary among patients. A deeper understanding of immune evasion is crucial for developing personalized treatments that can effectively engage the immune system to eliminate breast cancer. Dr. Betancur’s earlier research revealed the significance of super-enhancers in the genome—powerful clusters of enhancers spanning long genomic regions—that can increase the production of specific genes in a cancer cell. She found that in breast cancer cells, super-enhancers increase the levels of immune evasion genes including CD47. These genes encode proteins that block the immune response to cancer cells. Dr. Betancur’s AACR award supported by BCRF is focused on gaining a deeper understanding of super-enhancers’ role in breast cancer immune invasion.

What’s next

Recently, Dr. Betancur and her team identified an 8-base pair DNA variant within a genomic super-enhancer located between the genes CD47 and LINC00636 and discovered that the insertion controls pathways used by the tumor to suppress the immune system. Intriguingly, they found that the insertion variant is more common in European than in Asian populations, aligning with breast cancer rates in these groups. Next, Dr. Betancur seeks to understand whether this DNA insertion, when in an active breast cancer super-enhancer, triggers immune evasion by regulating the CD47 and LINC00636 genes. Revealing genomic signatures of immune evasion will enable personalized treatments that recruit the immune system to eradicate cancer.