Cancer-specific myelopoiesis

Cancer alters the normal pathways of myeloid cells development, leading to the accumulation of suppressor cells that dampen the immune response against the tumor, according to a report published this week in Nature Immunology.

Polymorphonuclear (PMN) cells and monocytes are two types of myeloid cells that develop from a common parent cell via divergent pathways. Tumor-bearing humans and mice show a dramatic expansion of myeloid cells - M-MDSC (monocytic-myeloid derived suppressor cells) and PMN-MDSCs - that have distinct functions. These cells were believed to differentiate along the same developmental pathways as monocytes and PMN cells. Dmitry Gabrilovich and colleagues show that in cancer M-MDSCs directly differentiate into PMN-MDSCs through downregulation of Rb1, a transcription factor known to control cellular proliferation and differentiation.

Identification of M-MDSCs as precursors of PMN-MDSCs could have important implications in cancer therapy, where MDSCs are known to negatively regulate anti-tumor immunity and promote tumor growth and metastasis.