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Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
Chemo-immunotherapy combinations have been regarded as one of the most practical ways to improve immunotherapy response in cancer patients. In this study, we integrated the transcriptomics data from immunotherapy-treated tumors and compound-treated cell lines to systematically identify chemo-immunot...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543256/ https://www.ncbi.nlm.nih.gov/pubmed/37790509 http://dx.doi.org/10.21203/rs.3.rs-3290264/v1 |
Sumario: | Chemo-immunotherapy combinations have been regarded as one of the most practical ways to improve immunotherapy response in cancer patients. In this study, we integrated the transcriptomics data from immunotherapy-treated tumors and compound-treated cell lines to systematically identify chemo-immunotherapy synergisms and their underlying mechanisms. Through analyzing anti-PD-1 treatment induced expression changes in patient tumors, we developed a shift ability score that can measure whether a chemotherapy treatment shifts anti-PD-1 response. By applying the shift ability analysis on 41,321 compounds and 16,853 shRNA treated cancer cell line expression profiles, we characterized a systematic landscape of chemo-immunotherapy synergism and prioritized 17 potential synergy targets. Further investigation of the treatment induced transcriptomic data revealed that a mitophagy-dsRNA-MAVS-dependent activation of type I IFN signaling may be a novel mechanism for chemo-immunotherapy synergism. Our study represents the first comprehensive effort to mechanistically characterize chemo-immunotherapy synergism and will facilitate future pre-clinical and clinical studies. |
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