Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion DOI Creative Commons
Victoria Roulstone, Joan Kyula, James C. Wright

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 25, 2025

Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen synergistic drug-virotherapy combinations and find that the reovirus type III Dearing strain (Rt3D)-palbociclib combination augments oncolytic virus-induced stress responses increases interferon production signaling. Data from RIG-I agonist ER stress-inducing agents further confirms crosstalk between RNA-sensing in inducing cancer cell death production. Combined Rt3D-palbociclib also innate immune activation IFN-induced HLA expression within tumor cells, with accompanying alterations epigenetic landscape endogenous retroviral (ERV) elements. Analysis immunopeptidome treated cells reveals changes to HLA-captured peptides, including altered peptides or testis antigens ERVs. Our findings thus highlight signaling PRR mediating enhanced anti-cancer efficacy.

Language: Английский

Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion DOI Creative Commons
Victoria Roulstone, Joan Kyula, James C. Wright

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 25, 2025

Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen synergistic drug-virotherapy combinations and find that the reovirus type III Dearing strain (Rt3D)-palbociclib combination augments oncolytic virus-induced stress responses increases interferon production signaling. Data from RIG-I agonist ER stress-inducing agents further confirms crosstalk between RNA-sensing in inducing cancer cell death production. Combined Rt3D-palbociclib also innate immune activation IFN-induced HLA expression within tumor cells, with accompanying alterations epigenetic landscape endogenous retroviral (ERV) elements. Analysis immunopeptidome treated cells reveals changes to HLA-captured peptides, including altered peptides or testis antigens ERVs. Our findings thus highlight signaling PRR mediating enhanced anti-cancer efficacy.

Language: Английский

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