Targeting TBK1 to overcome resistance to cancer immunotherapy.

ABSTRACT: Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking^1,2. Here we identify the innate immune kinase TANK-binding kinase 1 (TBK1)³ as a candidate immune-evasion gene in a pooled genetic screen⁴. Using a suite of genetic and pharmacological tools across multiple experimental model systems, we confirm a role for TBK1 as an immune-evasion gene. Targeting TBK1 enhances responses to PD-1 blockade by decreasing the cytotoxicity threshold to effector cytokines (TNF and IFNγ). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spher

SUBMITTER: Sun Y 

PROVIDER: S-EPMC10171827 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature