Metabolic stress related immune alterations with impact on graft-versus-leukemia effect in allogeneic stem cell transplantation (A06)

• Subject Area: Hematology, Oncology ; Gastroenterology ; Immunology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 324392634

During the first funding period (FP), we showed that patients undergoing allo-HSCT display signs of oxidative stress on the systemic as well as on the single cell level including T-cells. Oxidative stress led to DNA damages and T-cells with high levels of oxidative DNA damage displayed various dysfunctions and were associated with a significantly increased risk for relapse. In the second FP we aim to (A) validate oxidative DNA damage in T-cells as a biomarker for relapse risk, to (B) understand the underlying mechanisms (e.g. role of DNA repair genes, interplay between metabolism and repair), and to (C) develop strategies for bolstering DNA damage repair in T-cells as a means to improve GvL effect.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 221: Modulation of graft-versus-host and graft-versus-leukemia immune responses after allogeneic stem cell transplantation
• Applicant Institution: Universität Regensburg
• Project Heads: Professor Dr. Andreas Mackensen; Professor Dr. Dimitrios Mougiakakos