Tumor and Microenvironment Modification during Progression of Murine Orthotopic Bladder Cancer

Figure 3

A schematic diagram that summarizes the gene expression changes and immune cells identified in bladders after tumor implantation. Proliferating tumor cells increase the expression of GMCSF and CXCL10 which in turn recruit immune cells such as natural killer (NK) cells, dendritic cells (DC), macrophages, and T cells to the bladder. Increased expression and production of IFNγ, TNFα, IL12a, NOS2, and GZMB by the immune cells would inhibit tumor proliferation and induce apoptosis. Transcription factor GATA3 was downregulated, suppressing the production of TH2 T cells. CTLA4 binds to CD80 and inhibits T-cell activation. Upregulation of PTGS2 in either tumor or immune cells or both would have an inhibitory effect on immune cells. Downregulation of AGTR2 could have occurred in the tumor cells, normal bladder epithelia, or submucosa. The dotted arrow indicates that AGTR2 may cause apoptosis in tumor cells. Genes that are underlined were present at both day 7 and day 28. Genes in the shaded box were found only at day 28. Genes whose expression was upregulated are indicated by arrows pointing up, and those that were downregulated are indicated by arrows pointing down.