Epigenetics in T-cell driven inflammation and cancer

Abstract

For decades, scientists have been investigating how processes such as gene expression, stem cell plasticity, and cell differentiation can be modulated. The discovery of epigenetics helped unravel these processes and enabled the identification of major underlying mechanisms that, for example, are central for T cell maturation. T cells go through various stages in their development evolving from progenitor cells into double positive CD4/CD8 T cells that finally leave the thymus as naïve T cells. One major mechanism driving T cell maturation is the modulation of gene activity by temporally sequenced transcription of spatially exposed gene loci. DNA methylation, demethylation, and acetylation are key processes that enable a sequenced gene expression required for T cell differentiation. In vivo, differentiated T cells are subjected to enormous pressures originating from the microenvironment. Signals from this environment, particularly from an inflammatory or a tumor microenvironment, can push T cells to differentiate into specific effector and memory T cells, and even prompt T cells to adopt a state of dysfunctional exhaustion, en route of an epigenetically controlled mechanism. Fundamentals of these processes will be discussed in this review highlighting potential therapeutic interventions, in particular those beneficial to revive exhausted T cells.

Keywords: Anti-tumor vaccine; Epigenetics; ICI-treatment; T cell differentiation; T cell exhaustion.