Single-cell ATAC-seq maps the comprehensive and dynamic chromatin accessibility landscapes of human CAR-T cell exhaustion

Chimeric antigen receptor T cells (CAR-T) therapy has achieved remarkable therapeutic success in treating a variety of hematopoietic malignancies. However, the high relapse rate and poor in vivo persistence, partially caused by CAR-T cell exhaustion, are still important barriers against CAR-T therapy. It remains largely elusive on the mechanisms of CAR-T exhaustion and how to attenuate exhaustion to achieve better therapeutic efficacy. In this study, we performed scATAC-seq assays in CAR-T cells and illustrated the comprehensive dynamic changes of chromatin accessibility in CAR-T cells at the single cell level during CAR-T cells killing tumor cells both in vitro and in vivo.