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Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy

Background: The recent clinical success of immunotherapy represents a turning point in cancer management. But the response rate of immunotherapy is still limited. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, due to the lack of appropria...

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Autores principales: Wang, Ben, Liu, Mengmeng, Ran, Zhujie, Li, Xin, Li, Jie, Ou, Yunsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263059/
https://www.ncbi.nlm.nih.gov/pubmed/32528935
http://dx.doi.org/10.3389/fbioe.2020.00348
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author Wang, Ben
Liu, Mengmeng
Ran, Zhujie
Li, Xin
Li, Jie
Ou, Yunsheng
author_facet Wang, Ben
Liu, Mengmeng
Ran, Zhujie
Li, Xin
Li, Jie
Ou, Yunsheng
author_sort Wang, Ben
collection PubMed
description Background: The recent clinical success of immunotherapy represents a turning point in cancer management. But the response rate of immunotherapy is still limited. 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 single-cell RNA sequencing, we classified the tumor microenvironment into inflamed immunotherapeutic responsive and inflamed non-responsive. Then, phenotype-specific genes were identified to show mechanistic differences between distant microenvironment phenotypes. Finally, we screened for some potential drugs that can convert an unfavorable microenvironment phenotype to a favorable one to aid current immunotherapy. Results: Multiple signaling pathways were phenotypes-specific dysregulated. Compared to non-inflamed microenvironment, the expression of interleukin signaling pathways-associated genes was upregulated in inflamed microenvironment. Compared to inflamed responsive microenvironment, the PPAR signaling pathway-related genes and multiple epigenetic pathways-related genes were, respectively, suppressed and upregulated in the inflamed non-responsive microenvironment, suggesting a potential mechanism of immunotherapeutic resistance. Interestingly, some of the identified phenotype-specific gene signatures have shown their potential to enhance the efficacy of current immunotherapy. Conclusion: These results may contribute to the mechanistic understanding of immunotherapeutic resistance and guide rational therapeutic combinations of distant targeted chemotherapy agents with immunotherapy.
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spelling pubmed-72630592020-06-10 Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy Wang, Ben Liu, Mengmeng Ran, Zhujie Li, Xin Li, Jie Ou, Yunsheng Front Bioeng Biotechnol Bioengineering and Biotechnology Background: The recent clinical success of immunotherapy represents a turning point in cancer management. But the response rate of immunotherapy is still limited. 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 single-cell RNA sequencing, we classified the tumor microenvironment into inflamed immunotherapeutic responsive and inflamed non-responsive. Then, phenotype-specific genes were identified to show mechanistic differences between distant microenvironment phenotypes. Finally, we screened for some potential drugs that can convert an unfavorable microenvironment phenotype to a favorable one to aid current immunotherapy. Results: Multiple signaling pathways were phenotypes-specific dysregulated. Compared to non-inflamed microenvironment, the expression of interleukin signaling pathways-associated genes was upregulated in inflamed microenvironment. Compared to inflamed responsive microenvironment, the PPAR signaling pathway-related genes and multiple epigenetic pathways-related genes were, respectively, suppressed and upregulated in the inflamed non-responsive microenvironment, suggesting a potential mechanism of immunotherapeutic resistance. Interestingly, some of the identified phenotype-specific gene signatures have shown their potential to enhance the efficacy of current immunotherapy. Conclusion: These results may contribute to the mechanistic understanding of immunotherapeutic resistance and guide rational therapeutic combinations of distant targeted chemotherapy agents with immunotherapy. Frontiers Media S.A. 2020-05-25 /pmc/articles/PMC7263059/ /pubmed/32528935 http://dx.doi.org/10.3389/fbioe.2020.00348 Text en Copyright © 2020 Wang, Liu, Ran, Li, Li and Ou. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Wang, Ben
Liu, Mengmeng
Ran, Zhujie
Li, Xin
Li, Jie
Ou, Yunsheng
Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy
title Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy
title_full Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy
title_fullStr Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy
title_full_unstemmed Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy
title_short Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy
title_sort analysis of gene signatures of tumor microenvironment yields insight into mechanisms of resistance to immunotherapy
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263059/
https://www.ncbi.nlm.nih.gov/pubmed/32528935
http://dx.doi.org/10.3389/fbioe.2020.00348
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