RNA-seq in mouse CD8+ T cells cultured with medium with or without methionine

Abnormal epigenetic patterns correlate with effector T cell malfunction in tumors. However, their causal link is unknown. Here, we show that tumor cells disrupt methionine metabolism in CD8+ T cells, thereby lowering intracellular methionine levels and the methyl donor S-adenosylmethionine (SAM), resulting in loss of H3K79me2. Consequently, loss of H3K79me2 impaired T cell immunity. Our work reveals a novel mechanistic connection between methionine metabolism, histone patterns, and T cell immunity in the tumor microenvironment. Overall design: CD8+ T cells were cultured with fresh medium without methionine (fresh-), fresh medium with methionine (fresh+), B16F10 supernatants (Sup-), and B16F10 supernatants with methionine supplementation (Sup+) for 36h, quadruplicate per group.