Effects of targeted epigenetic modifications on T - cell reprogramming

Abstract Over the last decade there have been huge advances in DNA sequencing technology, allowing cancer patients to undergo genomic diagnosis within days of admission. Building upon genomic sequencing, epigenomic profiling approaches of tumor and infiltrating lymphocytes inform on the stage of the disease and immune response, but interpretation of these data remains hindered by issues of heterogeneity. Epigenetic programs, such as DNA methylation, play a vital role in the regulation of CD8+ T – cell development and differentiation. Here, we will investigate the effects of targeted epigenetic mechanisms on the function of effector memory T – cells. Hypomethylating agents, such as Decitabine, have been extensively used in myeloid malignancies including Acute Myeloid Leukemia and Myelodysplastic Syndromes; however, the impacts on T – cells have not been well studied. We hypothesize that the utilization of these epigenetic modifications will alter the function and phenotypic characteristics of the effector memory T – cells. These results will lead to new approaches for reprograming effector memory T – cells via removal of repressive DNA methylation. The outcome of this study will provide novel insight into our understanding of the epigenetic regulation of T – cells function; especially, how DNA methylation programs instilled during differentiation could be modified to improve T – cells function.