Unknown

Dataset Information

0

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 augments 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 engages both intrinsic and extrinsic apoptotic machinery upon exposure to TNF and IFN-γ. Our findings highlight HOIP inhibition as a potential strategy to harness and enhance the killing capacity of TNF and IFN-γ during immunotherapy.

SUBMITTER: Andrew Freeman 

PROVIDER: S-SCDT-EMBOR-2021-53391V1 | biostudies-other |

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC8567220 | biostudies-literature
| S-EPMC9479610 | biostudies-literature
| S-EPMC4877699 | biostudies-literature
| S-EPMC5066095 | biostudies-literature
| S-EPMC5874661 | biostudies-literature
| S-EPMC7770098 | biostudies-literature
| S-EPMC10608824 | biostudies-literature
| S-EPMC4893968 | biostudies-literature
| S-EPMC4758699 | biostudies-literature
| S-EPMC3701076 | biostudies-literature