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Genes 2017, 8(11), 308;

Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer

The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China
Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
College of Life Science, Tianjin Normal University, Tianjin 300384, China
Department of Medicine, McGill University, Montreal, QC H3A 0G4, Canada
These authors contribute equally to this work.
Authors to whom correspondence should be addressed.
Received: 4 October 2017 / Revised: 28 October 2017 / Accepted: 30 October 2017 / Published: 7 November 2017
(This article belongs to the Special Issue Integrative Genomics and Systems Medicine in Cancer)
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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. View Full-Text
Keywords: tumor infiltrated immune cells; regulatory network; network reprogramming tumor infiltrated immune cells; regulatory network; network reprogramming

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Han, P.; Gopalakrishnan, C.; Yu, H.; Wang, E. Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer. Genes 2017, 8, 308.

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