To evaluate the roles of IL-37 and IL-38 as endogenous regulators of CAR-T-associated hyperinflammation in multiple myeloma.
Approach:
Mechanistic Overview: The review discusses the mechanisms of cytokine release syndrome (CRS) in CAR-T therapy and the potential regulatory roles of IL-37 and IL-38.
Phase-Dependent Regulatory Axis: It proposes a regulatory axis where IL-38 limits inflammatory initiation and IL-37 suppresses systemic amplification during peak CRS.
Key Findings:
IL-37 functions primarily as a systemic mediator that suppresses NF-κB/MAPK signaling, inflammasome activity, and endothelial injury.
IL-38 acts as a tissue-resident regulator that restrains early innate immune priming and modulates macrophage-dendritic cell interactions within the bone marrow microenvironment.
These pathways represent promising immunoregulatory checkpoints with translational potential as biomarkers and therapeutic targets.
Interpretation:
Limitations:
The review is hypothesis-generating and does not propose immediate clinical applications.
Further research is needed to validate the roles of IL-37 and IL-38 in clinical settings.
Conclusion:
The study highlights the potential of IL-37 and IL-38 in managing CRS associated with CAR-T therapy in multiple myeloma.
