11.01.22

Fli-1 Regulates T Cell Immunity in GVHD

Schutt S, Wu Y, Kharel A, et al. The Druggable Transcription Factor Fli-1 Regulates T Cell Immunity and Tolerance in Graft-Versus-Host Disease. Journal of Clinical Investigation. 2022; (doi: 10.1172/JCI143950).

Friend Virus Leukemia Integration 1 (Fli-1), a transcription factor that differentially regulates CD4 versus CD8 T-cell response in the setting of graft-versus-host disease (GVHD), represents a potential treatment target for this life-threatening complication of allogeneic hematopoietic cell transplantation. Using single-cell RNA sequencing analysis, scientists discovered that Fli-1 promotes CD4 T-cell activity, including transcription of Th1 and Th17 pathways that are associated with GVHD pathogenesis. At the same time, Fli-1 suppresses CD8 T-cell activity that supports graft-versus-leukemia (GVL) function. The research demonstrated that a low dose of camptothecin, topotecan, or etoposide acts as a powerful Fli-1 blocker that simultaneously reduces GVHD severity and maintains the GVL effect. The concept was validated in a xenograft model that used human T cells to induce GVHD.

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