IFNγ Signaling in Natural and Therapy-Induced Antitumor Responses

IFNγ is a cytokine produced by a restricted number of immune cells that acts on every nucleated cell type. Consistent with this remarkably wide spectrum of targets, the effects of IFNγ are highly pleiotropic. On cells of the immune system, IFNγ signaling has generally a pro-inflammatory effect, coordinating the innate and adaptive responses. On nonimmune cells, IFNγ tends to exert the opposite effect; it inhibits cell proliferation, induces cell death, and, in addition, promotes their recognition by the immune system. These effects on the immune and nonimmune compartments play a crucial role during the immunoediting of tumors and, as shown by recent reports, also determine the efficacy of certain immunotherapies. Different therapeutic interventions to target IFNγ signaling are currently under way, and the emerging picture indicates that rewiring IFNγ signaling, disrupted in some cancer cells, may be an efficacious antitumor therapeutic strategy.