Macrophages Are Not Welcome: Potential of CCR1/CCR2 Inhibition for Cytokine Release Prevention

Chimeric antigen receptor (CAR) T cells can provide cures to patients affected by certain hematologic malignancies. Cytokine release syndrome (CRS) is a major side effect of this treatment, yet its pathophysiology remains incompletely understood and selective therapeutic options are limited. In this issue, Li and colleagues identify the CCR1-CCR2 axis as a key mediator of inflammatory macrophage recruitment to sites of CAR T-cell activation, thereby contributing to CRS. In preclinical models, blockade of this axis prevented macrophage recruitment and substantially diminished CRS severity. This discovery could open a new avenue for targeted intervention against CRS, although further validation of the role of the CCR1/CCR2 axis, particularly in clinically relevant settings, is required. See related article by Li and colleagues et al., p. XX.