Mechanism and effects of extramedullary hematopoiesis on anti-tumor immunity

Extramedullary hematopoiesis (EMH) in cancer. Tumor-induced inflammatory factors, such as GM-CSF, TNF-α, and IL-6, damage bone marrow erythropoiesis and upregulate erythrocyte apoptosis, causing anemia and EMH. Hematopoietic progenitor cells (HSPCs) are recruited to the spleen through upregulated CCL2/CCR2 signaling and differentiate into splenic myeloid-derived suppressor cells (MDSCs) under the combined action of splenic environmental factors and endogenous to perform immunosuppressive functions. Tumor-induced EMH-generated CD45⁻ erythroid progenitor cells (EPCs) promote tumor progression by secreting artemin. The CD45⁺ EPC population inhibits proliferation and immune function of CD8⁺ T cells by promoting overexpression of ROS, PD-L1, and Arg1, thus disrupting antitumor immunity. Furthermore, daughter cell EDMCs mediated by tumor-induced GM-CSF signals establish stronger immunosuppressive functions. (The figure was created with BioRender.com)