Fig. 1From: The evolution and heterogeneity of neutrophils in cancers: origins, subsets, functions, orchestrations and clinical applicationsThe evolution of neutrophils in humans. In humans, neutrophils originate from GMPs residing within the bone marrow, which are characterized by the expression of CD34, CD38, and CD45RA [29, 30]. Subsequently, these GMPs differentiate into pro-neutrophils (pro-neutrophil 1 and pro-neutrophil 2) and pre-neutrophils, expressing biomarkers such as CD11b, CD66b, and CD15 [31, 32]. This specific stage of neutrophil development, characterized by the presence of immature neutrophils exhibiting relatively high levels of biomarkers such as CD11b, CD16b, CD71, and CD117, has been duly acknowledged [26, 31, 33]. Ultimately, neutrophils that express chemokine receptors (CXCR)4 and CXCR2 undergo final maturation and are subsequently released into circulation. The C-X-C Motif Chemokine Ligand (CXCL)12 expressed by bone marrow stromal cells activates the neutrophil receptor CXCR4 to retain it within the bone marrow. While under the stimulation of G-CSF, endothelial cells in the bone marrow upregulate CXCL2 expression to activate CXCR2 signaling, thereby facilitating the releasing of neutrophils from the bone marrow into circulation [34, 35, 36]. Conversely, under pathological circumstances, the presence of mature neutrophils exhibiting abnormal biomarkers or immature neutrophils within the peripheral blood of humans has been reported [37, 35, 38]Back to article page