Multiorgan 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. Host cells derived from myeloid and lymphoid lineages perform well-established functions linked to cancer development, progression, and response to therapy. It is unclear whether host erythroid cells also contribute to shaping the path that cancer can take, but emerging evidence points to this possibility. Here, we show that tumor-promoting environmental stress and tumor-induced hemodynamic changes 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, such as the expression of both CD71 and TER119 and the retention of intact nuclei, and express genes encoding immune checkpoint molecules. Nucleated erythroid cells with similar properties are present in mouse and human tumor tissues. Antibody-mediated erythropoietin blockade reduces tumor-responsive erythroid cell induction and tumor growth. These findings reveal the potential of tumor-induced erythropoietin and erythroid cells as targets for cancer treatment.

Automated summary

Research has shown that tumor-promoting environmental stress and hemodynamic changes trigger erythropoietin production in the kidneys of mice, leading to the expansion of erythroid cell populations in the spleen. These erythroid cells exhibit specific molecular features and express genes encoding immune checkpoint molecules. Antibody-mediated erythropoietin blockade can reduce tumor growth, highlighting the potential of tumor-induced erythropoietin and erythroid cells as targets for cancer treatment.