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 some autoimmune diseases. Myeloid-derived macrophages play key roles in the pathogenesis of CRS, and participate in the production and release of the core CRS cytokines, including interleukin (IL)-1, IL-6, and interferon-γ. In this review, we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.