Inflammatory signaling drives SQSTM1-dependent suppression of interferon-γ-induced MHC class I

IL-1β suppresses IFN-γ–induced surface MHC-I expression in non-small cell lung cancer cells by accelerating MHC-I turnover 12–24 h after stimulation.

• Why it matters: Immune-inflamed tumors contain both IFN-γ and inflammatory cytokines, but the mechanisms by which cancer cells integrate these signals to regulate immunogenicity are unclear.
• What they did: NSCLC cells were stimulated with IFN-γ and IL-1β, with RNA sequencing showing selective induction of autophagy-related genes and imaging/biochemistry tracking MHC-I redistribution to autophagosome-lysosome compartments.
• The result: SQSTM1 is required for IL-1β–mediated MHC-I surface downregulation, while NBR1 depletion and autophagy or lysosomal inhibition did not restore MHC-I expression, linking inflammatory signaling to IFN-γ–MHC-I control via trafficking.