Inhibition of cancer cell NDUFS4 for antitumor immunity

Inhibiting cancer cell NDUFS4, a structural component of complex I of the mitochondrial electron transport chain, could help treat cancer by increasing levels of acetyl-CoA, which promotes histone acetylation that increases chromatin accessibility of HLA-I antigen presentation and processing machinery, thus enhancing antitumor immunity.

In immune-competent and immune-deficient syngeneic mouse models of melanoma, a tumor CRISPR/Cas9 loss-of-function screen of complex I subunit genes identified NDUFS4 as an immune-dependent mediator of tumor growth...