Immunotherapy With Human Gamma Delta T Cells-Synergistic Potential of Epigenetic Drugs?

Epigenetics has emerged as one of the fastest growing concepts, adding more than 45 new publications every day, spreading through various fields ( 1). Conrad Waddington coined the term “epigenetics” in 1942; however, a multitude of definitions has been endorsed by different researchers. In essence, Waddington’s definition of “epigenetics” and its redefinition by Holiday is at the heart of cellular function. Hence, it is obvious that epigenetic regulation plays a central role also in the specification, differentiation, and functional plasticity of T lymphocytes ( 2). T-cell fate decision in progenitor cells, functional CD4 T-cell plasticity, CD8 T-cell differentiation, but also T-cell memory, are all substantially governed by epigenetic mechanisms (3–7). Here, we focus on the current development of drugs targeting major pathways of epigenetic regulation and their possible impact on γδ T-cell multifunctionality. We aim to develop concepts of how some of these approaches might help to improve the efficacy of γδ T-cell-based immunotherapies