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Dr. Tobias Holderried

Ärztlicher Leiter Zentrum für Zelltherapie und  Stammzelltransplantation Bonn (ZZSB)

Dr. Holderried and his group focus on cellular immunoregulatory mechanisms and their role in steady state and disease. Of particular interest is the recently identified Qa-1 (HLA-E in man) restricted CD8+ regulatory T cell population (Treg), its impact on anti-tumor immune response and in Graft-versus-Host Disease (GvHD) following allogeneic stem-cell transplantation. The interactions of CD8+ Treg with other immune cells, notably additional regulatory cell subpopulations, play a major part in these analyses.

Immunosuppresion in the tumor-microenvironment induced by regulatory T cells has been shown to have a major impact on tumor behavior by allowing tumor escape, impairing the anti-tumor response in patients and constricting the success of immunotherapeutic options. In patients with Graft-versus-Host Disease Treg have shown in clinical trials to be an effective addition to current treatment regimens. The majority of studies addressing this issue, both in mice and humans, have focused on CD25+FOXP3+CD4+ regulatory T cells, which have led to many groundbreaking discoveries. However, the contribution of cellular mechanisms involved in regulatory CD8+ T cell-mediated immune responses has not been appreciated until recently.

Dr. Holderried’s group aims to further analyze the character of the cancer regulatory mechanisms of murine CD8+ Treg and their role in GvHD development and treatment. This knowledge is being used to identify the human homologue of the murine CD8+ Treg subpopulation. Close collaborations within the University Hospital allow translational assessment of human CD8+ Treg in malignant disease and during immune reconstitution after allogeneic stem-cell transplantation. The insights of this work should help to elucidate cellular immunoregulatory mechanisms by human CD8+ Treg and might lead to new immunotherapeutic approache