KLF2 protects T cells from exhaustion

In chronic infections and cancer, many T cells become “exhausted” — they lose their ability to divide and fight. A special subset, called stem-like T cells, can resist this process and are key to the success of immunotherapy.

In our recent Science paper, we discovered that the transcription factor KLF2 plays a central role in protecting these T cells. Without KLF2, stem-like cells collapse more quickly into exhaustion and fail to respond to checkpoint blockade therapy.

This work defines KLF2 as a molecular “guardian” of therapy-responsive T cells, and opens the door to new strategies that preserve the cells patients need for durable cancer immunity.

Impact:

  • First evidence that KLF2 is essential for sustaining stem-like T cells and driving effector functions.

  • Demonstrates that exhaustion program is repressed in T cells during acute infection.

  • Highlights role of KLF2 in T cell differentiation

DifferentiaitonNikhil JoshiT cell differentiation, CD8 T cells, LCMV infection