Oxygen levels at the time of activation determine T cell persistence and immunotherapeutic efficacy

Abstract

SummaryOxygenation levels are a determinative factor in T cell function. Here we describe that the oxygen tensions sensed by T cells at the moment of activation act to persistently modulate both differentiation and function. We found that in a protocol of CAR-T cell generation, 24 hours of low oxygen levels during initial CD8+T cell priming is sufficient to enhance antitumour cytotoxicity in a preclinical model. This is the case even when CAR-T cells are subsequently cultured under high oxygen tensions prior to adoptive transfer. Increased hypoxia inducible transcription factor (HIF) expression was able to alter T cell fate in a similar manner to exposure to low oxygen tensions; however, only a controlled or temporary increase in HIF signalling was able to consistently improve cytotoxic function of T cells. These data show that oxygenation levels during and immediately after T cell activation play an essential role in regulating T cell function.

Oxygen‐Releasing Hydrogels for Tissue Regeneration

“…are vital for tissue repair and infection control. [17] Moreover, fluctuating oxygen levels can modulate the activity of inflammatory cells, aiding in the maintenance of a balanced inflammatory response. [18] Oxygen also supports anti-infective mechanisms, empowering macrophages to eliminate pathogens and generating oxygen free radicals with antibacterial properties.…”