Cancer-specific myelopoiesis
Nature Immunology
January 28, 2013
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.
doi:10.1038/ni.2526
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