Researchers led by Ludwig Scientific Director Chi Van Dang and Adam Wolpaw, a postdoctoral fellow in Chi’s lab and a pediatric oncologist at Children’s Hospital of Philadelphia (CHOP), reported in a February publication in the Proceedings of the National Academy of Sciences how the epigenetic states assumed by neuroblastoma cells influence the tumor’s visibility to the immune system. Neuroblastoma cells alternate between two such functional states: the mesenchymal state—associated with cells responsible for recurrent disease, metastasis and chemotherapy resistance—and the far more common adrenergic state. Working with cell cultures of this cancer, Adam, Chi and their colleagues found that cells in the adrenergic state are unresponsive to double-stranded (ds) RNA, while those in the mesenchymal state respond to it readily with inflammatory signaling that can provoke immune responses. When exposed to a molecule named poly (I:C)—a mimic of dsRNA currently being evaluated in clinical trials—the inflammatory responses of mesenchymal cells made them susceptible to killing by the immune system’s T cells. Mouse studies confirmed that tumors composed of mesenchymal cells were far more infiltrated with immune cells. The findings have implications for the development of new strategies to treat drug resistant neuroblastoma tumors, and such efforts are already underway and will be spearheaded by Adam at CHOP.
This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).