Macrophage, the potential key mediator in CAR-T related CRS

• Main Authors: Zhaonian Hao, Ruyuan Li, Li Meng, Zhiqiang Han, Zhenya Hong
• Format: Article
• Language: English
• Published: BMC 2020-07-01
• Series: Experimental Hematology & Oncology
• Subjects: Chimeric antigen receptor T cell therapy; Cytokine release syndrome; Macrophage
• Online Access: http://link.springer.com/article/10.1186/s40164-020-00171-5

Abstract Chimeric antigen receptor (CAR) T cell therapy is a new frontier in cancer therapy. The toxicity of cytokine release syndrome (CRS) has become one of the major challenges that limits the wider use of CAR T cells to fight cancer. Exploration of CRS pathogenesis and treatment is becoming the main focus of ongoing studies. Myeloid-derived macrophages were found to play a critical role in CRS pathogenesis, and these cells mediate the major production of core cytokines, including IL-6, IL-1 and interferon (IFN)-γ. Colocalization of macrophages and CAR T cells was also identified as necessary for inducing CRS, and CD40L-CD40 signaling might be the key cell–cell interaction in the tumor microenvironment. Macrophages might also take part in endocrine and self-amplified catecholamine loops that can directly activate cytokine production and release by macrophages during CRS. In addition to tocilizumab and corticosteroids, several novel CRS therapies targeting macrophage-centered pathways have shown much potential, including GM-CSF blockade and administration of atrial natriuretic peptide (ANP) and α-methyltyrosine (metyrosine, MTR). In the present review, we summarized the role of macrophages in CRS and new developments in therapeutic strategies for CRS-associated toxicities.