Purpose of review
Chimeric antigen receptor (CAR)-T-cell therapy is a revolutionary tool in the treatment of cancer. CAR-T cells exhibit their effector functions through the recognition of their specific antigens on tumor cells and recruitment of other immune cells. However, this therapy is limited by the development of severe toxicities and modest antitumor activity in solid tumors. The host and tumor microenvironment interactions with CAR-T cells play an important role in orchestrating CAR-T-cell functions. Specifically, myeloid
lineage cells and their cytokines critically influence the behavior of CAR-T cells. Here, we review the specific effects of myeloid
cell interactions with CAR-T cells, their impact on CAR-T-cell response and toxicities, and potential efforts to modulate myeloid
cell effects to enhance CAR-T-cell therapy efficacy and reduce toxicities.
Independent studies and correlative science from clinical trials indicate that inhibitory myeloid
cells and cytokines contribute to the development of CAR-T-cell-associated toxicities and impairment of their effector functions.
These findings illuminate a novel way to reduce CAR-T-cell-associated toxicities and enhance their efficacy through the modulation of myeloid
lineage cells and inhibitory cytokines.