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Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer

The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown d...

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Autores principales: Han, Pengyong, Gopalakrishnan, Chandrasekhar, Yu, Haiquan, Wang, Edwin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704221/
https://www.ncbi.nlm.nih.gov/pubmed/29112124
http://dx.doi.org/10.3390/genes8110308
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author Han, Pengyong
Gopalakrishnan, Chandrasekhar
Yu, Haiquan
Wang, Edwin
author_facet Han, Pengyong
Gopalakrishnan, Chandrasekhar
Yu, Haiquan
Wang, Edwin
author_sort Han, Pengyong
collection PubMed
description The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown durable clinical effects on some patients with various advanced cancers. However, major gaps in our knowledge of immunotherapy have been recognized. To fill these gaps, we conducted a systematic analysis of the GRNs of key immune cell subsets (i.e., B cell, CD4, CD8, CD8 naïve, CD8 Effector memory, CD8 Central Memory, regulatory T, Thelper1, Thelper2, Thelp17, and NK (Nature killer) and DC (Dendritic cell) cells associated with cancer immunologic therapies. We showed that most of the GRNs of these cells in blood share key important hub regulators, but their subnetworks for controlling cell type-specific receptors are different, suggesting that transformation between these immune cell subsets could be fast so that they can rapidly respond to environmental cues. To understand how cancer cells send molecular signals to immune cells to make them more cancer-cell friendly, we compared the GRNs of the tumor-infiltrating immune T cells and their corresponding immune cells in blood. We showed that the network size of the tumor-infiltrating immune T cells’ GRNs was reduced when compared to the GRNs of their corresponding immune cells in blood. These results suggest that the shutting down certain cellular activities of the immune cells by cancer cells is one of the key molecular mechanisms for helping cancer cells to escape the defense of the host immune system. These results highlight the possibility of genetic engineering of T cells for turning on the identified subnetworks that have been shut down by cancer cells to combat tumors.
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spelling pubmed-57042212017-11-30 Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer Han, Pengyong Gopalakrishnan, Chandrasekhar Yu, Haiquan Wang, Edwin Genes (Basel) Article The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown durable clinical effects on some patients with various advanced cancers. However, major gaps in our knowledge of immunotherapy have been recognized. To fill these gaps, we conducted a systematic analysis of the GRNs of key immune cell subsets (i.e., B cell, CD4, CD8, CD8 naïve, CD8 Effector memory, CD8 Central Memory, regulatory T, Thelper1, Thelper2, Thelp17, and NK (Nature killer) and DC (Dendritic cell) cells associated with cancer immunologic therapies. We showed that most of the GRNs of these cells in blood share key important hub regulators, but their subnetworks for controlling cell type-specific receptors are different, suggesting that transformation between these immune cell subsets could be fast so that they can rapidly respond to environmental cues. To understand how cancer cells send molecular signals to immune cells to make them more cancer-cell friendly, we compared the GRNs of the tumor-infiltrating immune T cells and their corresponding immune cells in blood. We showed that the network size of the tumor-infiltrating immune T cells’ GRNs was reduced when compared to the GRNs of their corresponding immune cells in blood. These results suggest that the shutting down certain cellular activities of the immune cells by cancer cells is one of the key molecular mechanisms for helping cancer cells to escape the defense of the host immune system. These results highlight the possibility of genetic engineering of T cells for turning on the identified subnetworks that have been shut down by cancer cells to combat tumors. MDPI 2017-11-07 /pmc/articles/PMC5704221/ /pubmed/29112124 http://dx.doi.org/10.3390/genes8110308 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Pengyong
Gopalakrishnan, Chandrasekhar
Yu, Haiquan
Wang, Edwin
Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer
title Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer
title_full Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer
title_fullStr Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer
title_full_unstemmed Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer
title_short Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer
title_sort gene regulatory network rewiring in the immune cells associated with cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704221/
https://www.ncbi.nlm.nih.gov/pubmed/29112124
http://dx.doi.org/10.3390/genes8110308
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