BACKGROUND _ AIMS: The leukocyte composition of @entity5 is heterogeneous, as is the involvement of each leukocyte subset in promoting or restraining tumorigenesis. This heterogeneity reflects the tissue of origin, @entity5 stage, and the functional state of leukocyte activation, but its biological roots remain poorly understood. Since tumorigenesis is driven by various genetic events, we assessed the role of driver genes in shaping the profiles and the roles of leukocytes in tumorigenesis. METHODS: @entity19 @entity96 were induced by hepatic overexpression of either MYC or the combination of myristoylated AKT and @entity17226 ) oncogenes via hydrodynamic transfection. A comparative, flow cytometry- and histology-based immunophenotyping of liver-infiltrating leukocytes was performed at various stages of liver tumorigenesis. The roles of the most abundant leukocyte subsets in tumorigenesis were addressed by immunodepletion. The contribution of @entity99 was assessed by comparing the injury-inducing hydrodynamic transfection model to a model in which MYC is an inducible transgene. RESULTS: Myristoylated AKT and @entity17226 ) promoted a marked recruitment of @entity3804 (+) @entity17775 (hi) @entity19347 (int) neutrophils and @entity3804 (+) @entity17775 (-) @entity19347 (hi) monocytes to the liver, but their immunodepletion did not alter tumorigenesis. In contrast, despite minimal invasion by monocytes/neutrophils during MYC-driven tumorigenesis, immunodepletion of these cells reduced MYC @entity5 burden and extended survival. MYC-driven @entity5 initiation was augmented specifically by @entity19347 (+) monocytes and their ability to promote @entity99 . CONCLUSIONS: Our results demonstrate that leukocyte profiles do not necessarily predict their involvement in tumorigenesis, the functional role of leukocytes can be shaped by oncogenes, and that monocyte-dependent tissue injury selectively cooperates with MYC during tumorigenesis.

Monocyte-dependent XXXX promotes carcinogenesis in an oncogene-specific manner.

@entity17775 :: ('546644(Tax:10090)', 'Gene') :: ['Ly6G'] @entity96 :: ('MESH:D008113', 'Disease') :: ['liver tumors'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity19 :: ('10090', 'Species') :: ['Mouse'] @entity19347 :: ('17067(Tax:10090)', 'Gene') :: ['Ly6C'] @entity17226 :: ('18176(Tax:10090)', 'Gene') :: ['NRAS(V12'] @entity3804 :: ('16409(Tax:10090)', 'Gene') :: ['CD11b'] @entity99 :: ('MESH:D056486', 'Disease') :: ['liver injury']
@entity99 :: (MESH:D056486,Disease) :: ['liver injury']
