Immune checkpoint inhibitors — cancer therapies that remove the “brakes” on the adaptive anti-tumor immune response — have had remarkable success in melanoma and lung cancer. Response rates to these immunotherapies in breast cancer have been disappointing, perhaps because breast cancers are less “immunogenic” and contain fewer cancer-killing immune cells.
David Elion, Rebecca Cook, PhD, and colleagues are exploring approaches that activate innate immunity in breast cancer cells and the tumor microenvironment. They tested the use of a synthetic RIG-I agonist in breast cancer cells and in a mouse model of breast cancer. RIG-I is a virus-sensing receptor that activates proinflammatory signaling pathways.
Reporting in the journal Cancer Research, the team found that RIG-I agonist increased the expression of proinflammatory factors and triggered two forms of cell death (apoptosis and pyroptosis). In breast tumors in mice, RIG-I activation increased tumor lymphocytes and decreased tumor growth and metastasis.
The findings demonstrate that a RIG-I agonist has potent immunogenic and therapeutic effects in breast cancer.
This research was supported by grants from the National Institutes of Health (CA098131, CA068485, TR000445), the Congressionally Directed Medical Research Program, and the National Science Foundation.
