Pseudo-Exhaustion of CD8+ T cells in acute myeloid leukemia (AML)

Abstract

Event Abstract Back to Event Pseudo-Exhaustion of CD8+ T cells in acute myeloid leukemia (AML) Frauke M. Schnorfeil1, 2*, Katharina Emmerig1, 2, Julia Neitz1, 2, Felix S. Lichtenegger1, 2, 3, Rika Draenert4, Wolfgang Hiddemann2 and Marion Subklewe1, 2 1 Helmholtz Zentrum München, Clinical Cooperation Group Immunotherapy, Germany 2 Klinikum der Universität München, Department of Internal Medicine III, Germany 3 Klinikum der Universität München, Division of Clinical Pharmacology, Germany 4 Klinikum der Universität München, Division of Infectious Diseases, Germany The prognosis of acute myeloid leukemia (AML) is poor due to high relapse rates after induction chemotherapy. Dendritic cell (DC)-based immunotherapy is a promising strategy to stimulate AML-specific immunity, particularly T cells. However, the functionality of T cells in AML patients is not well described. T cell exhaustion, characterized by an increased expression of inhibitory molecules and funtional deficits, has been suggested to contribute to immune evasion in various solid and hematological malignancies. To characterize T cell exhaustion in AML, CD8+ T cell surface expression of CD244, CD160, PD-1 and TIM-3 as well as proliferation and cytokine production were measured. Results were compared to healthy controls (HCs) and untreated HIV-infected patients. To specify the stimulatory effect of DCs on AML patient-derived T cells, we cocultured DCs with autologous T cells. We detected increased frequencies of CD244+, CD160+ and PD-1+ CD8+ T cells in HIV patients, while AML patients at time of diagnosis and relapse or during refractory disease had higher frequencies of CD244+ and TIM-3+ or PD-1+ CD8+ T cells, respectively. However, no functional impairment of AML patient-derived T cells was observed so far. DC stimulation resulted in upregulation of PD-1 and TIM-3, accompanied by high IFNγ secretion, that could be enhanced by PD-1 blockade. Thus, we found elevated levels of exhaustion-associated inhibitory molecules on CD8+ T cells of AML patients, which were further upregulated upon DC stimulation. Our data suggest that immunotherapeutic strategies combining DC vaccination and immunomodulatory antibodies directed against T cell inhibitory molecules are particularly suited for AML treatment. Keywords: Immunotherapy, t cell exhaustion, AML, Dendritic Cells, immunomodulatory antibodies Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Schnorfeil FM, Emmerig K, Neitz J, Lichtenegger FS, Draenert R, Hiddemann W and Subklewe M (2013). Pseudo-Exhaustion of CD8+ T cells in acute myeloid leukemia (AML). Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01189 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Frauke M Schnorfeil, Helmholtz Zentrum München, Clinical Cooperation Group Immunotherapy, Munich, Germany, frauke.schnorfeil@helmholtz-muenchen.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe Google Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe Google Scholar Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe PubMed Frauke M Schnorfeil Katharina Emmerig Julia Neitz Felix S Lichtenegger Rika Draenert Wolfgang Hiddemann Marion Subklewe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.