Histone Deacetylase Inhibitors and IL21 Cooperate to Reprogram Human Effector CD8⁺ T Cells to Memory T Cells.

ABSTRACT: Clinical response rates after adoptive cell therapy (ACT) are highly correlated with in vivo persistence of the infused T cells. However, antigen-specific T cells found in tumor sites are often well-differentiated effector cells with limited persistence. Central memory CD8⁺ T cells, capable of self-renewal, represent desirable ACT products. We report here that exposure to a histone deacetylase inhibitor (HDACi) and IL21 could reprogram differentiated human CD8⁺ T cells into central memory-like T cells. Dedifferentiation of CD8⁺ T cells was initiated by increased H3 acetylation and chromatin accessibility at the CD28 promoter region. This led to IL21-mediated pSTAT3 binding to the CD28 region, and subsequent upregulation of surface CD28

SUBMITTER: Wang J 

PROVIDER: S-EPMC7269845 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature