title: T cells are functionally not impaired in AML: increased PD-1 expression is only seen at time of relapse and correlates with a shift towards the memory T cell compartment.
abstract: BACKGROUND
  T cell function is crucial for the success of several novel immunotherapeutic strategies for the treatment of acute myeloid leukemia (AML). However, changes in phenotype and function of T cells have been described in various hematologic malignancies, mimicking T cell exhaustion known from chronic viral infections. Detailed knowledge about phenotype and function of T cells in AML patients at different stages of the disease is indispensable for optimal development and application of immunotherapeutic strategies for this disease.
  
  
  METHODS
  We used flow cytometry-based assays to characterize T cell phenotype and function in peripheral blood and bone marrow of AML patients at diagnosis, at relapse after intensive chemotherapy, and at relapse after allogeneic stem cell transplantation (SCT). Surface expression of CD244, PD-1, CD160, and TIM-3 was determined, and proliferation and production of IFN-γ, TNF-α, and IL-2 were measured.
  
  
  RESULTS
  We detected similar expression of inhibitory molecules on T cells from patients at diagnosis and from age-matched healthy controls. At relapse after SCT, however, PD-1 expression was significantly increased compared to diagnosis, both on CD4(+) and CD8(+) T cells. This pattern was not associated with age and cytomegalovirus (CMV) status but with a shift towards effector memory cells in relapsed AML patients. Proliferation and cytokine production assays did not reveal functional defects in T cells of AML patients, neither at diagnosis nor at relapse.
  
  
  CONCLUSIONS
  We thus conclude that T cell exhaustion does not play a major role in AML. Immunotherapeutic strategies targeting autologous T cells thus have particularly good prospects in the setting of AML.
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. frauke.schnorfeil@helmholtz-muenchen.de.|Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany. frauke.schnorfeil@helmholtz-muenchen.de.
authors.forename: Frauke M
authors.initials: FM
authors.lastname: Schnorfeil
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. felix.lichtenegger@med.uni-muenchen.de.|Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany. felix.lichtenegger@med.uni-muenchen.de.|Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Universität München, Munich, Germany. felix.lichtenegger@med.uni-muenchen.de.
authors.forename: Felix S
authors.initials: FS
authors.lastname: Lichtenegger
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. kathi_emmerig@gmx.de.|Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany. kathi_emmerig@gmx.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Emmerig
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. miriam-schlueter@gmx.de.|Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany. miriam-schlueter@gmx.de.
authors.forename: Miriam
authors.initials: M
authors.lastname: Schlueter
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. julia.s.neitz@gmail.com.|Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany. julia.s.neitz@gmail.com.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Neitz
authors.affiliation: Division of Clinical Infectiology, Department of Internal Medicine IV, Klinikum der Universität München, Munich, Germany. rika.draenert@med.uni-muenchen.de.
authors.forename: Rika
authors.initials: R
authors.lastname: Draenert
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. wolfgang.hiddemann@med.uni-muenchen.de.|Clinical Cooperation Group Pathogenesis of Acute Myeloid Leukemia, Helmholtz Institute Munich, Munich, Germany. wolfgang.hiddemann@med.uni-muenchen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. marion.subklewe@med.uni-muenchen.de.|Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany. marion.subklewe@med.uni-muenchen.de.
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology*; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism*; D012008:Recurrence
chemical_list: D061026:Programmed Cell Death 1 Receptor