Yin and yang of tumor inflammation: How innate immune suppressors shape the tumor microenvironments

Abstract

Pattern recognition-mediated sensing systems direct host immunity towards either antitumor immunosurveillance or protumorigenic inflammation. These activities imply dual and conflicting roles in the regulation of tumor-associated inflammation. On the one hand, recent evidence has revealed that several signaling components and cell-surface receptors suppress innate immune signals and constitute a negative feedback machinery preventing excess and continuous inflammation within tumor microenvironments. On the other hand, these same components also negatively regulate intrinsic tumorigenic activities by targeting nuclear factor-kappaB (NF-κB)-mediated antiapoptotic and inflammatory signals. Furthermore, the activation status of innate immune suppressors may reflect the functional plasticity of interactions between tumor cells and innate immune cells and determine whether tumor inflammation supports anti- or pro-tumorigenic responses. Thus, innate immune suppressors may provide valuable information about the immunogenic or tumorigenic status of tumor-associated inflammation thereby serving as potential biomarkers that predict tumor progression. Comprehensive analysis for identifying general and unique features of each innate immune suppressor in the regulation of tumor inflammation should explore the development of new biomarkers for improving future therapeutic strategies. © 2013 UICC.