Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model

Abstract

Cancer tissue is frequently associated with the host inflammatory response, which involves blood cells. Using DNA microarrays, we examined the gene expression profiles of blood and tumors in a murine subcutaneous hepatocellular carcinoma model, in which tumors develop during the initial 10 days and then diminish and disappear by day 25 after implantation. Immunohistochemical and gene expression analysis indicated that tumor tissues were associated with an active immune response, particularly the CD4+ T cell-mediated immune response, on day 10. The genes commonly up-regulated in blood and the fraction enriched with tumor-associated inflammatory cells on day 10 also suggested the involvement of CD4+ T cells. Unsupervised hierarchical clustering analysis of gene expression of peripheral blood cells on days 0, 10, 15, 20, and 25 indicated two major clusters: the tumor-existence cluster on days 10, 15, and 20, and the tumor-free cluster on days 0 and 25. Additionally, sub-clusters were detected on each day. These results suggest that the gene expression profile of whole blood cells is affected by the local tumor condition, and is associated with the local host immune response. Its analysis will facilitate exploration of the underlying important features of the host immune response to tumors.