TNF and melanoma: Tumor-cell killing by T cells requires the pro-apoptotic effects of perforin and granzymes, death receptors, and/or IFNs.59,60 To evolve resistance to killing by ICI-invigorated T cells, melanoma CNVs downregulated both extrinsic and intrinsic programmed cell-death mechanisms, attenuating IFN-γ–tumor necrosis factor alpha (TNF-α)–FAS immunogenic effector signaling and tumor-cell-intrinsic BAD-BAX-APAF1-CASP9 signaling.