HOIP limits anti-tumor immunity by protecting against combined TNF and IFN-gamma-induced apoptosis.

ABSTRACT: The success of cancer immunotherapy is limited to a subset of patients, highlighting the need to identify the processes by which tumors evade immunity. Using CRISPR/Cas9 screening, we reveal that melanoma cells lacking HOIP, the catalytic subunit of LUBAC, are highly susceptible to both NK and CD8⁺ T-cell-mediated killing. We demonstrate that HOIP-deficient tumor cells exhibit increased sensitivity to the combined effect of the inflammatory cytokines, TNF and IFN-γ, released by NK and CD8⁺ T cells upon target recognition. Both genetic deletion and pharmacological inhibition of HOIP augment tumor cell sensitivity to combined TNF and IFN-γ. Together, we unveil a protective regulatory axis, involving HOIP, which limits a transcription-dependent form of cell death that en

SUBMITTER: Freeman AJ 

PROVIDER: S-EPMC8567220 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature