Double-edged roles of IFN in tumor elimination and immune escape

Interferon-gamma (IFN gamma) is a pleiotropic cytokine implicated in tumor immune surveillance, with its antiproliferative, pro-apoptotic, and immune-provoking effects. Regarding the antitumor effects of IFN gamma, IFN gamma-dependent therapies have been proposed and have undergone many clinical trials for various cancer types but the outcomes were not satisfactory. Recent studies have suggested that cancer cells develop immune evasion strategies to escape from IFN gamma-dependent immunosurveillance by various mechanisms. In this review, we summarize recent advances in the effects and molecular mechanisms of IFN gamma on target cells, as well as potential immune escape mechanisms of tumor cells. Furthermore, we discuss how to target IFN gamma signaling and overcome immune evasion to provide promising therapeutic strategies for the treatment of patients with cancer.