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Immune checkpoint blockade lowers the threshold of naïve T-cell priming to drug-associated antigens in a dose-dependent fashion.

Sophie GriceKaty SaideLiam FarrellGeorgia WellsCatherine BettsSean HammondDean John Naisbitt
Published in: Toxicological sciences : an official journal of the Society of Toxicology (2024)
A growing body of clinical and experimental evidence indicates that immune checkpoint blockade enhances patient susceptibility to hypersensitivity reactions to co-administered medications. In this study, we utilized an in vitro T-cell priming assay to demonstrate one of the mechanistic hypotheses on how this occurs; through lowering of the threshold in patients to elicit aberrant T-cell responses. We outline the dependency of de novo T-cell priming responses to drug-associated antigens on dose at initial exposure. Findings support the aforementioned hypothesis and offer an experimental representation of fundamental parameters at play in hypersensitivity reactions to low molecular weight compounds.
Keyphrases
  • drug induced
  • end stage renal disease
  • chronic kidney disease
  • newly diagnosed
  • dendritic cells
  • peritoneal dialysis
  • adverse drug
  • emergency department
  • case report
  • patient reported outcomes