Bulk RNA sequence and bulk ATAC sequence of treated murine CD8+ T cells

We identify that GSH maintains the function of CD8+ T cell and GSH metabolism is interacting with A2AR signaling pathway to reshape the metabolism and anti-function in CD8+ T cell. We found A2AR signaling blockade leads to the upregulation of GSH metabolism related genes and loss of the genes abolishes the benefits from A2AR antagonist on CD8+ T cells. Considering to the essential role of GSH metabolism in ferroptosis, we combined the potent ferroptosis inhibitor liproxstatin-1 (Lip-1) and A2AR antagonist (SCH58261) to treat CD8+ T cells. Notably, our combination therapy significantly promotes the anti-tumor immunity of CD8+ T cells with delayed tumor growth in tumor bearing mice. Examination of gene profile in CD8+ T cells from tumor bearing mice treated with or without anti-CD73; or from in vitro 7-days culture with SCH58261 (A2ARi), Lip-1 or A2ARi/Lip-1 treatment