PRF1 and hemophagocytic syndrome: In the absence of perforin, CAR T-cells may undergo re-expansion and subsequently produce heightened levels of proinflammatory cytokines, such as GM-CSF, TNF-α, and IFN-γ, which ultimately result in the initiation of an inflammatory cascade reaction and the subsequent onset of delayed HLH following CRS resolution [115] (Fig. 3).