Titles and Affiliations
Assistant Professor
Department of Radiation Oncology
American Association for Cancer Research
Research area
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 when presented to immune cells, prevent them from destroying 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.
Progress Thus Far
Recently, Dr. Betancur and her team identified a DNA variant that controls pathways used by the tumor to suppress the immune system. Intriguingly, they found that the variant is more common in European than in Asian and African populations, aligning with breast cancer rates in these groups. Dr. Betancur and her team found that removing this variant from breast cancer cells increased the activity of both target genes, delayed cancer cell death, and reduced the infiltration of pro-inflammatory macrophages—immune cells typically involved in attacking tumors. This reduction suggests that the tumor may become more effective at evading the immune system. The team also discovered that removing this variant turned on a group of genes in cancer cells that are known to drive tumor growth, therapy resistance, and immune suppression. These effects were largely driven by the increased activity of LINC00636, a gene that is not yet well understood in breast cancer. Importantly, they found that patients who carry this variant tend to have better progression-free survival, suggesting that it may offer some protection against aggressive tumor behavior.
What’s next
Over the coming year, Dr. Betancur and her team will work to better understand the role of this DNA variant by studying it in breast cancer models with or without it. The team will engineer macrophages that are tagged with a fluorescent marker, then image the cells in the models to analyze the extent of macrophage infiltration.
Biography
Paola Betancur, PhD is an expert in gene regulation and immunogenomics. She received her undergraduate degree from Stony Brook University, NY in biology, and her PhD from Caltech in cell biology. Dr. Betancur completed postdoctoral training at Stanford University, in the laboratory of Dr. Irv L. Weissman, where she studied the genomic mechanisms that activate an immune evasion program in cancer cells through CD47 upregulation. She joined the University of California, San Francisco as faculty in 2019.
