Issues

IFNγ blockade provides shelter from the cytokine storm during chimeric antigen receptor (CAR) T-cell therapy. On page 90, McNerney et al. bring the topic In Focus with a discussion on the role of IFNγ in cytokine release syndrome (CRS) and related hyperinflammatory conditions. Illustrating the topic is a unique case of a leukemia patient receiving anti-IFNγ for refractory CRS following CAR-T therapy and achieving sustained clinical remission. On page 136, Bailey et al. report that genetic or pharmacologic IFNγ blockade does not impair CAR-T activity against blood cancers while reducing CRS-associated macrophage and cytokine responses in pre-clinical models. Although often used as an indicator of CAR-T activity, IFNγ may instead be dispensable in cases of hematologic malignancies and indeed be a promising target to treat CAR T–mediated CRS without sacrificing clinical response.