FOXO1 is a master regulator of CAR T memory programming

Area of Science:

• Immunology
• Cell Biology
• Cancer Research

Background:

• CAR T cell therapy persistence is limited, hindering treatment for B cell malignancies and solid tumors.
• Memory gene expression, like TCF7 (TCF1), is crucial for CAR T cell response and long-term persistence.
• Understanding the regulators of CAR T cell memory and exhaustion is critical for enhancing therapeutic efficacy.

Conclusions:

• FOXO1 acts as a key pioneer transcription factor that promotes memory programs and restrains exhaustion in human CAR T cells.
• FOXO1-mediated memory reprogramming can significantly enhance the persistence and potency of CAR T cells for cancer immunotherapy.
• Targeting pioneer factors like FOXO1 represents a promising strategy for optimizing therapeutic T cell states and improving clinical outcomes.