Rosalie M Sterner1,2,3, Saad S Kenderian2,3,4,5. 1. Mayo Clinic Medical Scientist Training Program, Mayo Clinic College of Medicine and Science. 2. Department of Immunology. 3. T Cell Engineering. 4. Department of Molecular Medicine. 5. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
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. RECENT FINDINGS: 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. SUMMARY: 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.
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. RECENT FINDINGS: 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. SUMMARY: 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.