Abstract
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.
Highlights
The human body has an intricate ability to combat genetic disorders such as cancer
T cells play an active role in combating cancer cells, while B cells play an innate role in attacking cancer cells
Cancer cells may send out molecular signals that can modify the gene regulatory networks of the major immune cells
Summary
The immune system could combat cancer cells by recognizing cancer cells and killing them via sophisticated molecular mechanisms [1]. The immune system has different types of immune cells, which have different functions [2,3]. T cells play an active role in combating cancer cells, while B cells play an innate role in attacking cancer cells. Cancer cells bypass immunological suppression and proliferate uncontrollably [4]. In this process, cancer cells may send out molecular signals that can modify the gene regulatory networks of the major immune cells. Cancer cells may send out molecular signals that can modify the gene regulatory networks of the major immune cells
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