Mar 20, 2020

Analysis of genetic signatures of tumor microenvironment yields insight into mechanisms of resistance to immunotherapy

Ben WangYunsheng Ou


Background: Therapeutic intervention targeting immune cells have led to remarkable improvements in clinical outcomes of tumor patients. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, due to the lack of appropriate experimental methods, the reason why the immunotherapeutic resistance still existed on the inflamed tumor microenvironment remains unclear. Materials and methods: Here, based on integrated single-cell RNA sequencing technology, we classified tumor microenvironment into inflamed immunotherapeutic responsive and inflamed non-responsive. Then, phenotype-specific genes were identified to show mechanistic differences between distant TME phenotypes. Finally, we screened for some potential favorable TME phenotypes transformation drugs to aid current immunotherapy. Results: Multiple signaling pathways were phenotypes-specific dysregulated. For example, Interleukin signaling pathways including IL-4 and IL-13 were activated in inflamed TME across multiple tumor types. PPAR signaling pathways and multiple epigenetic pathways were respectively inhibited and activated in inflamed immunotherapeutic non-responsive TME, suggesting a po...Continue Reading

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Mentioned in this Paper

Administration of Antineoplastic Agent
Genetic Markers
Molecular Genetic Technique
Epigenetic Process
Transmissible Mink Encephalopathy
Multiple Tumors

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