Understanding and targeting erythroid progenitor cells for effective cancer therapy

It is well described that tumor-directed aberrant myelopoiesis contributes to the generation of various myeloid populations with tumor-promoting properties. A growing number of recent studies have revealed the importance of the previously unappreciated roles of erythroid progenitor cells (EPCs) in the context of cancer, bringing the updated concept that altered erythropoiesis also facilitates tumor growth and progression. Better characterization of EPCs may provide attractive therapeutic opportunities.

EPCs represent a heterogeneous population. They exhibit crucial pro-tumor activities by secreting growth factors and modulating the immune response. Cancers induce potent EPC expansion and suppress their differentiation. Recent single-cell transcriptome and lineage tracking analyses have provided novel insight that tumor-induced EPCs are able to be transdifferentiated into immunosuppressive myeloid cells to limit T-cell function and immunotherapy. Therapeutic strategies targeting key factors of EPC-driven immunosuppression, reducing the amount of EPCs, and promoting EPC differentiation and maturation have been extensively investigated.

This review summarizes the current state of knowledge as to the fascinating biology of EPCs, highlights mechanisms by which they exert the tumor promoting activities, as well as the perspectives on future directions and strategies to target these cells for potential therapeutic benefit.