Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion.

ABSTRACT: Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen for synergistic drug-virotherapy combinations and find that the reovirus type III Dearing strain (Rt3D)-palbociclib combination augments oncolytic virus-induced stress responses and increases interferon production and signaling. Data from RIG-I agonist and ER stress-inducing agents further confirms the crosstalk between RNA-sensing and ER stress in inducing cancer cell death and interferon production. Combined Rt3D-palbociclib also increases innate immune activation and IFN-induced HLA expression within tumor cells, with accompanying alterations in the epigenetic landscape and endogenous retroviral (ERV) elements. Analysis of the immunopepti

SUBMITTER: Roulstone V 

PROVIDER: S-EPMC12103499 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature