IFNG and cancer: However, numerous studies have demonstrated that IFNs also play important roles in protecting a host against tumor development through their direct effects on target cells and by activating immune responses.237 IFNγ exerts indirect effects on tumor cells via the TME and modulation of the immune response,238 and type I IFNs exert direct effects (on cancer cells) and indirect effects (through immune effector cells and vasculature) on tumors.239 However, their systemic toxicities and short half-life following administration limit their overall bioavailability.240