Multi-organ signaling mobilizes tumor-associated erythroid cells expressing immune checkpoint molecules

Hematopoietic-derived cells are integral components of the tumor microenvironment and serve as critical mediators of tumor-host interactions. Cells derived from myeloid and lymphoid lineages perform well-established functions linked to cancer development, progression and response to therapy. It is unclear whether erythroid cells exert such host cell functions in cancer, but emerging evidence points to this possibility. Here we show that tumor-promoting environmental stress and tumor-induced physiological disruption trigger renal erythropoietin production and erythropoietin-dependent expansion of splenic erythroid cell populations in mice. These erythroid cells display molecular features indicative of an immature erythroid phenotype and express immune checkpoint molecules. Erythroid cells with similar properties are present in mouse and human tumor tissues. Antibody-mediated erythropoietin blockade or erythroid cell depletion reduces tumor growth. These findings reveal the potential of erythropoietin and erythroid cells as targets for cancer treatment.