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The development of CRS after CAR-T cell therapy. The triggering mechanisms are incompletely understood, but CRS is triggered by the release of immunostimulatory cytokines (e.g., IFN-γ, TNF-α) both from the tumor cells and CAR-T cells. Immunocompetent cells as well as stromal cells (e.g., endothelial cells) are subsequently activated and thereby release excessive amounts of proinflammatory cytokines as the final part of a positive feedback loop.
