Epigenetic modification and its promise in cancer

The study of inherited changes in gene expression that do not include changes in DNA sequence (Lucas, 2017). The changes in expression can be induced by numerous factors like the environment and a person’s lifestyle. These factors effect DNA methylation, histone modification, histone variants, and acetylation. Modification to gene expression can be transmitted to daughter cells, also experiments have shown that the modification can be reversed (Weinhold, 2006). Why is this important for the topic of cancer? First, I should explain the following terms; tumor microenvironment (TME), chemokines, and programmed death-ligand 1 (PD-L1). TME is a complex environment of benign and malignant cells, immune cells, and normal cells. They often include immune cells that have been manipulated by the tumor and acquire immunosuppressive properties (van der Woude, Lieke L. et al., 2017). Chemokines are proteins secreted by cells used for signaling. Immune cells have chemokine receptors that will bind to these secreted proteins. This helps the immune cells to migrate toward targets and with regulation of immune cells. Like chemokines, PD-L1 is found on cells. T cells will have specific receptors that will bind PD-L1, as a result T cell activity is suppressed. This mechanism protects non-cancerous/toxic cells in our body.  Where does epigenetics fall in this conversation?

Modification explain earlier can alter the composition of the TME. Certain chemokines CXCL9 and CXCL10 are upregulated in tumor cells and results in T cells unable to penetrate the TME. Histone modification and DNA methylation of cancer cells resulted in downregulation of the chemokines discussed earlier allowing for better infiltration of T cells (van der Woude, Lieke L. et al., 2017). Cancer cells upregulate PD-L1 which downregulates T cells and modification in cancer cells helped with the obstruction of the PD-L1 and T cell receptor activity. The goal is to increase T cell penetration to help fight the cancer cells.

Weinhold, B. (2006, March). Epigenetics: The Science of Change. Retrieved Novemeber 25, 2017, from https://ncbi.nlm.nih,gov/pmc/articles/PMC1392256

Van der Woude, Lieke L. et al., (2017, November). Migrating into the Tumor: a Roadmap for T cells. Retrieved November 25, 2017, from http://www.cell.com/trends/cancer/fulltext/S2405-8033(17)30192-9