Application of Epigenetics in T & CAR-T Cell Research
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Epigenetics refers to heritable changes in gene expression without changes in the DNA sequence, including DNA methylation, histone modification, chromosomal remodeling, and non-coding RNA. Changes in T cell phenotypes are programmed epigenetically to transform into different T cell states. For example, DNA methylation and histone modification play important roles in biological phenomena such as determining the correct T cell lineage, different CD4+ Th phenotypes are partly due to epigenetic regulation, and epigenetic regulation mechanisms establish and maintain effector function in memory cells to ensure the rapid immune response to secondary antigens and so on. Chimeric antigen receptor T (CAR-T) cells, as an adoptive cell transfer therapy, have achieved great success in the treatment of cancer (such as acute leukemia) or viral infections (such as HIV). However, it is still unclear whether CAR-T application is safe in clinic, so epigenetic processes in T and CAR-T cells should be investigated in detail. In this review, we will focus on key epigenetic processes involved in T cell polarization, differentiation, exhaustion, and memory formation, as well as epigenetic approaches to enhance CAR-T therapy.
Epigenetics, CD4+ and CD8+ lineage, differentiation, polarization, exhaustion, CAR T cells