Scientists at Louisiana State University Health New Orleans say they have identified the crucial role the Chop inflammatory protein plays in the body's ability to fight cancer. Results demonstrate, for the first time, that Chop regulates the activity and accumulation of cells that suppress the body's immune response against tumors, according to the researchers.
The LSU Health New Orleans research team showed that when they removed Chop, the T cells of the immune system mounted an effective attack on the cancer cells. These findings reveal Chop as a target for the development of new immunotherapies to treat cancer.
The research is described in a paper (“The Stress-Response Sensor Chop Regulates the Function and Accumulation of Myeloid-Derived Suppressor Cells in Tumors”) published in Immunity.
Myeloid-derived suppressor cells (MDSCs) are involved in cancer, inflammation, and infection. MDSCs not only inhibit the immune response that destroys cancer cells, but they also promote the growth of new blood vessels that feed tumors, as well as the spread of cancer.
“Although we know what MDSCs do, very little has been known about what governs how they function,” noted Paulo Rodriguez, Ph.D., assistant research professor of microbiology, immunology, and parasitology at LSU Health New Orleans' Stanley S. Scott Cancer Center. “This has limited the development of strategies to block the harmful activity of MDSCs.”
The LSU Health research team discovered that the stress sensor C/EBP-homologous protein (Chop) regulates the function of MDSCs. They learned how Chop is distributed within the tumor environment in different types of cancer. They also determined how Chop controls tumor growth. The team confirmed their findings by deleting Chop and studying the effect. They found that the absence of Chop not only reduced the ability of MDSCs to inhibit T cells and suppress immune response, but also boosted the effectiveness of treatment.
“Chop-deficient MDSCs displayed reduced signaling through CCAAT/enhancer-binding protein-β, leading to a decreased production of interleukin-6 (IL-6) and low expression of phospho-STAT3. IL-6 overexpression restored immune-suppressive activity of Chop-deficient MDSCs,” wrote the investigators. “These findings suggest the role of Chop in tumor-induced tolerance and the therapeutic potential of targeting Chop in MDSCs for cancer immunotherapy.”