Figure S1. Skin exposure to UVB induces splenic erythroid cell proliferation in mice. Figure S2. Skin exposure to UVB results in expansion of splenic cell populations with erythroid colony-forming potential. Figure S3. Administration of an anti-EPO antibody prevents UVB-responsive splenic erythroid expansion. Figure S4. Tumor growth induces splenic erythroid cell proliferation in mice. Figure S5. CD235A immunostaining identifies tumor-associated erythroid cells in human cancer tissues.
ARTICLE ABSTRACT
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.
: Our study identifies erythropoietin and erythroid cells as novel players in tumor–host interactions and highlights the involvement of multiorgan signaling events in their induction in response to environmental stress and tumor growth.
