Inhibition of TBK1/IKKε mediated RIPK1 phosphorylation sensitizes tumors to immune cell killing.

ABSTRACT: Resistance to immune cell-mediated cytotoxicity poses a significant challenge in cancer therapy, compromising the efficacy of immunotherapeutic approaches such as immune checkpoint blockade (ICB) treatment. To enhance therapy outcomes, it is crucial to identify interventions that can synergize with ICB therapy to overcome tumor resistance. Therefore, we need to define the cellular mechanisms that sensitize tumors to cytotoxic T cells. CD8 T cells rely on cytokines such as TNF to carry out their cytotoxicity against tumors, and recent findings link select tumor mutations in the TNF pathway to increased T cell killing, in a manner dependent on RIPK1 kinase. Here, we demonstrate that sensitized tumor cells fail to initiate inhibitory RIPK1 phosphorylation at site S25 upon T cell attack, there

SUBMITTER: Piskopou A 

PROVIDER: S-EPMC12663160 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature