Figure 5.
Enhanced metabolic signature in effector Tconv cells precedes breakthrough GVHD after posttransplant cyclophosphamide. Metabolic hallmarks of aGVHD after PTCy further the role for Tconv in the process. (A) GSEA using hallmark datasets from the MSigDb highlights dominantly enhanced metabolic signatures, including OXPHOS, Glycolysis, and fatty acid metabolism in Tconv (red) over CD8+T cells (blue) in matched donor alloBMT patients developing aGVHD. (B-C) Hallmarks of augmented metabolic function in aGVHD are seen in Tconv recovered from aGVHD patients early before disease development (aGVHD n = 8; GVHD-free n = 7; healthy control n = 6). (B) Expression of TOMM20 (essential for import and assembly of respiratory chain complexes) and VDAC (mitochondrial porin essential for OXPHOS and glycolysis coupling), and (C) GLUT1, a key glucose transporter, and hexokinase 2, an enzyme catalyzing glucose phosphorylation, was quantified in patient samples at defined time points after alloBMT. Cumulative scaled MFI data for all time points and heatmap highlighting individual patient changes on day 28 is shown.