Escape from IFN-γ-dependent immunosurveillance in tumorigenesis

Immune interferon ( IFN), also known as IFN-gamma, promotes not only immunomodulation but also antimicrobial and anticancer activity. After IFN-gamma binds to the complex of IFN-gamma receptor ( IFNGR) 1-IFNGR2 and subsequently activates its downstream signaling pathways, IFN-gamma immediately causes transcriptional stimulation of a variety of genes that are principally involved in its biological activities. Regarding IFN-gamma-dependent immunosurveillance, IFN-gamma can directly suppress tumorigenesis and infection and/ or can modulate the immunological status in both cancer cells and infected cells. Regarding the anticancer effects of IFN-gamma, cancer cells develop strategies to escape from IFN-gamma-dependent cancer immunosurveillance. Immune evasion, including the recruitment of immunosuppressive cells, secretion of immunosuppressive factors, and suppression of cytotoxic T lymphocyte responses, is speculated to be elicited by the oncogenic microenvironment. All of these events effectively downregulate IFN-gamma-expressing cells and IFN-gamma production. In addition to these extrinsic pathways, cancer cells may develop cellular tolerance that manifests as hyporesponsiveness to IFN-gamma stimulation. This review discusses the potential escape mechanisms from IFN-gamma-dependent immunosurveillance in tumorigenesis.