Tumor methionine metabolites reprograms chromatin accessibilities of CD8+ T cells linking to T cell dysfunction.

T-cell exhaustion denotes a hypofunctional state of T lymphocytes commonly found in cancer, but how tumor cells drive T-cell exhaustion remains elusive. We found oncogenic reprograming of HCC methionine recycling with elevated 5-methylthioadenosine (MTA) and S-adenosylmethionine (SAM) to be tightly linked to T-cell exhaustion. We used an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to assay the genome-wide chromatin accessibility of T cells during activation and SAM/MTA treatment. Overall design: ATAC-sequencing was performed on non-activated CD8+ T cell and activated CD8+ T cells with and without SAM or MTA treatment.