REVIEWCancer-Associated Myeloproliferation: Old Association, New Therapeutic Target
Section snippets
MYELOID-DERIVED SUPPRESSOR CELLS
Myeloid-derived suppressor cells are a heterogeneous population of immature myeloid cells that are functionally defined by their ability to suppress host anti-tumor immunity.28, 29 The expansion of these cells is mediated by tumor- and stromal-derived factors that drive myelopoiesis and inhibit myeloid differentiation, including hematopoietic (eg, colony-stimulating factors [CSF]) and inflammatory (eg, interleukin [IL] 1, IL-6) cytokines, arachidonic acid metabolites, damage-associated
MYELOID CELLS AND TUMOR ANGIOGENESIS
Tumor- and stromal-derived proangiogenic factors promote formation of the tumor vasculature that is required for tumor growth and progression.80 Vascular endothelial growth factor A (VEGF-A) is a well-characterized factor that promotes tumor angiogenesis.81 Vascular endothelial growth factor A neutralization mediated by the monoclonal antibody bevacizumab inhibits tumor growth and angiogenesis in tumor xenografts and is now widely used in various human malignancies.80, 81 Tumor-infiltrating
THERAPEUTIC TARGETING OF CANCER-ASSOCIATED MYELOPOIESIS: TURNING TUMOR IMMUNITY “ON” AND ANGIOGENESIS “OFF”
Because tumor-associated myeloid cells, including MDSCs, suppress host anti-tumor immunity and promote tumor angiogenesis, targeting these cells represents a novel therapeutic approach in human cancers. The list of tumor-associated factors that drive myelopoiesis in the tumor-bearing host and promote activation, recruitment, and effector function of these myeloid cells continues to expand and presents many opportunities for therapeutic targeting of these cells. In contrast, the outright
CONCLUSION
Chronic inflammation has been implicated in the development of neoplastic disease for almost 150 years.141 Since then, many epidemiological and animal studies support this association.142 In the modern era, the association between malignant diseases, particularly when metastatic or locally advanced, and development of a leukocytosis has been appreciated, even though the importance of this association remained obscure. However, a growing body of work demonstrates that carcinogenesis and tumor
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