Fig. 5. PD-1 regulates the differentiation and lineage fate commitment of myeloid progenitors during cancer-mediated emergency myelopoiesis and determines the efficiency of T cell antitumor responses.

(A) During cancer-driven emergency myelopoiesis, PD-1 is up-regulated on CMPs but mostly in GMPs and inhibits signaling and metabolic reprogramming mediated by growth factors driving emergency myelopoiesis, resulting in accumulation of immature myeloid cells and immunosuppressor MDSCs, and decreased systemic output of effector myeloid cells. (B) PD-1 ablation in myeloid cells promotes signaling and metabolic reprogramming mediated by growth factors of emergency myelopoiesis and leads to the output of effector myeloid cells with improved antigen-presenting function that drive T effector memory cell responses and antitumor protection. HSC, hematopoietic stem cell; CMP, common myeloid progenitor; GMP, granulocyte/monocyte progenitor; MDP, monocyte/dendritic cell progenitor; CDP, common dendritic cell progenitor; DC, dendritic cell; CSF, cancer-produced soluble factor.