Figure 2.

The underlying mechanisms of CRS and ICANS. CAR-T cells produce cytokine storm, which activates bystander immune cells. When CD40L on CAR-T cells interacts with CD40 on immune cells and endothelial cells, an inflammatory response occurs, with interleukin-6 (IL-6) playing a major role in the cytokine release positive feedback loop, compromising vascular integrity. The perforin produced by CAR-T cells induces tumor pyroptosis, releasing danger-associated molecular patterns (DAMPs). CAR-T cells, immune cells, and cytokines can penetrate the disrupted blood–brain barrier (BBB) and trigger inflammatory reactions in the central nervous system (CNS), resulting in neuronal injury.