Immune therapy focused on harnessing CD8+ T cells has emerged as a powerful tool for treating cancer. Indeed, immune therapy has been instated as the fourth pillar of cancer therapy next to surgery, chemo and radio therapy. Naïve CD8+ T cells are activated upon antigen encounter followed by proliferation, expansion and differentiation into CD8+ T Effector cells. For prolonged immunity, a pool of CD8+ T Memory cells will persist after the source of antigen has been cleared. Importantly, Memory CD8+ T cells possess features of both naïve and effector cells, maintaining pluripotency with the ability to rapidly respond to a secondary infection by expanding and adopting effector functions. Pre-clinical experiments have demonstrated that Memory T cells provide superior anti-tumour activity when transferred into tumour bearing mice. These observations highlight the need for a better understanding of memory T cell formation and identifying avenues to promote this subtype on a molecular level. Transcriptional control of the transition of naïve CD8 T cells into memory and effector cells is a process well studied whereas the epigenetic mechanisms driving these gene expression changes have yet to be fully understood. Using a novel inhibitor of histone acetyl transferases we demonstrate that epigenetic rewiring during the activation process of naïve T cells leads to a larger proportion of Memory CD8 T cells. In this project we focus on understanding the role of epigenetic rewiring and the differentiation process of T cells to improve immune therapies in cancer using targeted and unbiased screening approaches.