Oxygen starvation during T cell priming boosts cancer-killing potential

Immune-based tumor-therapy has seen substantial progress in recent years and has made important inroads in the fight against cancer. Checkpoint inhibitors are a clinical success and the use of cell-based therapy models is rapidly expanding. T cells, such as chimeric antigen receptor T cells (CARs) and tumor infiltrating lymphocytes (TILs), are now routinely cultured and activated in labs and subsequently adoptively transferred to patients with the aim of reducing and eradicating tumors. However, although positive results have been obtained in clinical trials, immune rejection of tumors is often not successful. This has focused attention on improving delivery and cytotoxic potential of transferred cells. Gropper et al. (1), now show that culturing CD8 T cells under hypoxic conditions, during in vitro priming and prior to adoptive transfer, enhances their cytolytic capacity resulting in more robust anti-tumor activity in a murine cancer model. These findings could have implications for the future of T cell-based tumor therapies and may improve the design of protocols aimed at potentiating cytotoxicity prior to adoptive transfer of T cells