Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells which normally regulate immune response and tissue repair. In cancer, however, they are exploited within the tumor microenvironment to suppress T cell immune response. Patients observed to have an elevated population of MDSCs tend to have worse outcomes.
A University of Michigan-led team studying triple-negative breast cancer (TNBC) has now gained a new understanding of how a key metabolic pathway that promotes the development of MDSCs. Their work has been published in Cell Metabolism.
In studying human cell cultures of TNBC, the team observed a high activity in aerobic glycolysis, a known hallmark of cancer. When they restricted glycolysis, this resulted in a similar inhibition of a certain protein known as LAP. It turns out, LAP directly regulates a cellular signaling pathway that leads into the development of MDSC. From in vivo experiments that inhibited glycolysis, the team found “enhanced T cell immunity, reduced tumor growth and metastasis, and prolonged mouse survival.”
The team concludes that collectively, tumor glycolysis impacts cancer immunity and patient outcome through MDSCs.
"We don't have many treatment options for triple-negative breast cancer. One of the immunological reasons may be that these tumors have a large number of myeloid suppressor cells. This could be an issue. We hope that by understanding the biology better, it may lead to new ways to help these patients," says senior study co-author Weiping Zou.