Ex vivo conditioning with IL-12 protects tumor-infiltrating CD8 + T cells from negative regulation by local IFN- γ

In this report, we further elucidate the mechanism of this potency, showing that IL-12 additionally counteracts the negative regulatory effects of autocrine IFN-γ. IL-12 not only downregulates PD-1 expression by T cells, thus minimizing the effects of IFN-γ-induced PD-L1 upregulation by tumor stromal cells, but also inhibits IFNγR2 expression, thereby protecting T cells from IFN-γ-induced cell death. Thus, the enhanced anti-tumor activity of CD8+ T cells expanded ex vivo in the presence of IL-12 is due not only to the ability of IL-12-stimulated cells to secrete sustained levels of IFN- γ, but also to the additional capacity of IL-12 to counter the negative regulatory effects of autocrine IFN-γ. (Source: Cancer Immunology, Immunotherapy)

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