Researchers have discovered that advanced tumors can manipulate the metabolism of erythroid progenitor cells (EPCs), a type of immature red blood cell, to suppress the body’s immune response. In many cancer patients, tumors stimulate the production of these cells outside the bone marrow, mainly in the spleen. Some EPCs enter the tumor microenvironment where they strongly suppress immune activity, while others remain in the spleen and release signaling molecules that weaken immune defenses throughout the body.
The study found that tumors reprogram EPC metabolism to block immune attacks through several mechanisms. Certain EPCs produce large amounts of reactive oxygen species, which damage T-cell receptors and prevent T cells from recognizing cancer cells. These cells also consume the amino acid arginine using the enzyme arginase-1, depriving T cells of a nutrient they need to function and multiply. In addition, related immune cells derived from EPCs can express PD-L1, a protein that shuts down CD8⁺ T cells, while EPCs also release TGF-β, a molecule that suppresses natural killer cells and dendritic cells and promotes regulatory T cells that protect tumors.
Scientists believe that targeting the metabolism and activity of EPCs could improve cancer immunotherapy. Proposed strategies include reducing the number of EPCs by forcing them to mature into normal red blood cells, blocking their migration from the spleen to tumors, selectively eliminating them with antibody-drug conjugates or radiation, and restoring immune function using arginase-1 inhibitors or molecules that neutralize reactive oxygen species. Researchers also suggest that EPC levels or their metabolic products could serve as biomarkers to predict responses to immunotherapy, although translating these findings from animal models to human clinical trials remains a challenge.