The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment
Abstract
:1. Introduction
2. Epigenetics Plays a Key Role in Th17 Cells Lineage Commitment and Plasticity
2.1. Epigenetic Initiation of the Th17 Differentiation Program
2.2. Th17 Plasticity
3. The Influence of the Tumor Microenvironment on the Epigenome of the Tumor Infiltrating Lymphocytes (TILs)
3.1. Pro-Tumoral Function of Th17 Cells
3.2. Anti-Tumoral Function of Th17 Cells
4. Epigenetic Factors Leading to Th17 Cell Predominance in the TME (Tumor Micro-Environment)
4.1. The Cytokines Produced by the TME Drive the Th17 Polarization and Expansion
4.2. Epigenetics May Enhance Th17 Recruitment or Inhibit the Recruitment of Other CD4 T Cells at the Tumor Site
4.3. Modification of the Epigenome by the Tumor Micro-Environment
4.3.1. The Hypoxic Tumor Microenvironment
4.3.2. Metabolism
4.4. Th17 Predominance in Tumor Can Be Modulated by Plasticity
4.4.1. Treg to Th17 Cell Plasticity
4.4.2. Th17 to Th1 Cell Plasticity
5. The Promising Use of Epidrugs in Combination with Other Therapies for Anti-Tumor Treatment
5.1. Combination of Immune Checkpoint Blockade with Epidrugs
5.2. Favoring Tumor Immunogenicity with Epidrugs
5.3. Remodeling of the Tumor Micro-Environment by Epidrug Treatment
6. Epigenetic Reprogramming of CD4 T Cells to Modulate Th17 Cell Differentiation and Plasticity
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Genes | Epigenetic Regulation | Factors Modulating the Epigenome | References | |
---|---|---|---|---|
Th17 differentiation | IL-17, RORγt | Histone modification complex like HAT or HMT responsible for the deposition of permissive marks | Cytokines of the TME | [9,10,12,13,14,15,16,17,60,61,62,74,75,76,77,80,81,82] |
DNA demethylation enzymes (5hmc) | Metabolism regulates the biodisponibility of co-factors of epigenetic enzymes | |||
miRNA | Metabolites produced by gut microbiota modulate epigenetic enzymes activity | |||
Th17 recruitment through the CCR6-CCL20 axis | CCL20 | long non coding RNA (lncRNA-u50535) | Upregulation of lncRNA-u50535 in colorectal cancer | [64] |
Th17 plasticity | [74,75,76,77,79,88] | |||
- Th17 /Treg plasticity | Foxp3 | DNA methylation | Glutamate Metabolism pathway (reduction of 2 hydroxyglutarate level in Th17 cells diminish the Foxp3 promoter methylation status) | |
- Th17/Th1 cells plasticity | IFN-γ, Tbet | Histone modification complex | Exposition of differentiated Th17 cells to another cytokinic environment |
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Renaude, E.; Kroemer, M.; Loyon, R.; Binda, D.; Borg, C.; Guittaut, M.; Hervouet, E.; Peixoto, P. The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment. Int. J. Mol. Sci. 2020, 21, 1673. https://doi.org/10.3390/ijms21051673
Renaude E, Kroemer M, Loyon R, Binda D, Borg C, Guittaut M, Hervouet E, Peixoto P. The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment. International Journal of Molecular Sciences. 2020; 21(5):1673. https://doi.org/10.3390/ijms21051673
Chicago/Turabian StyleRenaude, Elodie, Marie Kroemer, Romain Loyon, Delphine Binda, Christophe Borg, Michaël Guittaut, Eric Hervouet, and Paul Peixoto. 2020. "The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment" International Journal of Molecular Sciences 21, no. 5: 1673. https://doi.org/10.3390/ijms21051673