Reference - Detail
| RRC ID | 84425 |
|---|---|
| Author | Roulstone V, Kyula-Currie J, Wright J, Patin EC, Dean I, Yu L, Barreiro-Alonso A, Melake M, Choudhary J, Elliott R, Lord CJ, Mansfield D, Matthews N, Chauhan R, Jennings V, Chan Wah Hak C, Baldock H, Butera F, Appleton E, Nenclares P, Pederson M, Foo S, Wongariyapak A, Rullan A, Tenev T, Meier P, Vile R, Pandha H, Melcher A, McLaughlin M, Harrington KJ. |
| Title | Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion. |
| Journal | Nat Commun |
| 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 immunopeptidome in treated cells further reveals changes to HLA-captured peptides, including altered expression of peptides from cancer or testis antigens and ERVs. Our findings thus highlight the crosstalk between stress signaling and PRR activation for mediating enhanced anti-cancer efficacy. |
| Volume | 16(1) |
| Pages | 4855 |
| Published | 2025-5-25 |
| DOI | 10.1038/s41467-025-60133-5 |
| PII | 10.1038/s41467-025-60133-5 |
| PMID | 40413207 |
| PMC | PMC12103499 |
| MeSH | Antineoplastic Agents* / pharmacology Cell Line, Tumor DEAD Box Protein 58 / metabolism Endoplasmic Reticulum Stress* / drug effects Humans Immune Evasion* / drug effects Immunity, Innate / drug effects Interferons / metabolism Neoplasms* / immunology Neoplasms* / therapy Oncolytic Viruses Piperazines* / pharmacology Pyridines* / pharmacology RNA, Double-Stranded* / genetics RNA, Double-Stranded* / metabolism Receptors, Immunologic Receptors, Pattern Recognition / metabolism Signal Transduction / drug effects |
| IF | 12.121 |
| Resource | |
| Mice | RBRC05737 |