Figure 6.

IFN-γ activity and modulators in tumors with different immune cell reliance.

In NK cell-dependent tumor models, IFN-γ was shown to cause resistance through the up-regulation of MHC class I, irrespective of ICB treatment. Conversely, in highly CD8+ T cell-dependent models, IFN-γ has more disparate effects depending on ICB treatment. In particular, in the absence of ICB, IFN-γ causes PD-L1-mediated immune resistance. PD-L1 blocking antibodies break this resistance, leaving largely antitumor effects of IFN-γ.

ICB, immune checkpoint blockade; IFN-γ, interferon-γ; MHC, major histocompatibility complex; NK, natural killer; PD-L1, programmed death-ligand 1.