Figure 1. Senescence-inflammatory response in epithelium.
A. Oncogene-induced senescence (OIS) in hepatic tumor cells, through secretion of SASP-factor CCL2, stimulates natural killer (NK) cell-mediated anti-tumor immune responses.
B. Using a model of NrasG12V-driven, OIS, senescent premalignant hepatocytes stimulate immune surveillance by secretion of SASP factors. SASP factors results in the activation of CD4+, TH1 cells, which subsequently limit liver cancer development via macrophage/monocyte mediate clearance.
C. PTEN-loss induced senescent prostate tumor cells promote cancer progression by the SASP factor-mediated establishment of immunosuppressive inflammation. In this model, Jak2/Stat3 dependent SASP factor expression results in recruitment of CD11b+Gr-1+ myeloid cells which limit cytotoxic T cell (CTL) function and thus tumor growth is unrestrained.
D. In a model of colorectal cancer, a SASP related secretory profile, termed the senescence-associated inflammatory response (SIR), is secreted by stressed epithelial cells. The SIR promotes tumorigenesis following the loss of p53 expression. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) can reverse the tumor promoting effects of the SIR.
