Abstract 393: Dynamic networks of transcriptome, DNA methylome, and DNA hydroxymethylome during T-cell lineage commitment

Abstract

Abstract Immunotherapy is a treatment that uses a part of a personal immune system to overcome diseases such as cancer. T cell therapy has been used in a variety of cancer types, including lymphoma, melanoma and colon cancer. There are several strategies used to take advantage of cell-mediated anti-tumor properties of T cells. Cellular immune responses to prevent tumors are typically caused by CD4 and CD8 T cells. The stepwise development of T cells from a multipotent precursor is guided by diverse mechanisms including interactions of lineage specific transcription factors and epigenetic changes and acquires lineage-specific trait. However, in this T-cell development process, a greater understanding of the regulation of genes involved in immunotherapy is needed. To elucidate the transcriptional networks and epigenetic mechanisms underlying T-cell therapy and T cell lineage commitment, we investigated genome-wide changes in gene expression, DNA methylation and hydroxymethylation among five successive populations of T cell development (DN3, DN4, DP, CD4+, and CD8+) using RNA-seq, MBD-seq and hMeDIP-seq, respectively. And investigated interactive networks of transcription factors, chromatin modifiers, and DNA methylation. We found stage specific differentially methylated regions and some of them occurred near the specific differentially expressed genes related to immune cells or cancer immunotherapy such as Cd4, Ccr9 and Pdcd1. Dynamic changes of DNA methylation and hydroxymethylation is associated with the recruitment of the stage specific transcription factors. This study may provide a frame work for understanding the complexity of T cell lineage commitment and immunotherapy-related genes were regulated during T-cell differentiation. Citation Format: Byoung-Ha Yoon. Dynamic networks of transcriptome, DNA methylome, and DNA hydroxymethylome during T-cell lineage commitment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 393.