Focused evaluation of the roles of macrophages in chimeric antigen receptor (CAR) T cell therapy associated cytokine release syndrome

Cytokine release syndrome (CRS) is a major obstacle to the widespread clinical application of chimeric antigen receptor (CAR)T cell therapies. CRS can also be induced by infections (such as SARS-CoV-2), drugs (such as therapeutic antibodies), and someautoimmune diseases. Myeloid-derived macrophages play key roles in the pathogenesis of CRS, and participate in the productionand release of the core CRS cytokines, including interleukin (IL)-1, IL-6, and interferon-γ. In this review, we summarize the roles ofmacrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulationin CRS.