Targeting the Hypoxic Microenvironment in Cutaneous Chronic Graft-Versus-Host Disease Through PI3Kδ Inhibition

The study investigates the role of the hypoxic microenvironment in cutaneous chronic graft-versus-host disease (cGVHD) and explores the therapeutic potential of PI3Kδ inhibition. Using a murine model, researchers found that cGVHD skin lesions are characterized by a hypoxic immune environment driven by IL-13, activating the PI3K-AKT signaling pathway. The study identified four key cell types contributing to cGVHD skin lesions and demonstrated that PI3Kδ inhibition, using Parsaclisib, significantly reduced cGVHD symptoms, including hair loss, skin fibrosis, and improved survival rates. The findings suggest that targeting the hypoxic milieu with PI3Kδ inhibitors could be a promising therapeutic strategy for cGVHD.