Fig. 6. Proposed model of aberrant neutrophil differentiation in the spleen during cancer.
Myeloid cells differentiate in bone marrow from hematopoietic stem cells through common myeloid progenitors. Common granulocyte/monocyte progenitors expand in the bone marrow and migrate to spleen as a marginated pool, where they give rise to normal neutrophil maturation and, in cancer, aberrant neutrophil differentiation into G-MDSCs. Our findings that indicate MDSC-specific gene signature that is largely shared between G- and M-MDSCs but differs from their normal myeloid counterparts. This MDSC signature includes numerous chemokine receptors, which likely guide their migration towards primary tumor or metastatic sites (indicated by arrows), where they may shield tumor cells from anti-tumor immunity.