title: Longitudinal analyses of leukemia-associated antigen-specific CD8+T cells in patients after allogeneic stem cell transplantation.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment approach for patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Graft versus leukemia (GVL) effects, which are exerted by donor T cells directed against leukemic-associated antigens (LAAs), are considered to play a crucial role in disease eradication. Although the expansion of cytotoxic T lymphocytes (CTLs) specific for cytomegalovirus (CMV) in response to an infection has been shown in multiple studies, data on CTLs mediating GVL effects are limited. To evaluate a potential increase or decrease of T lymphocytes specific for LAAs in the setting of allogeneic HSCT, we monitored leukemia-specific CD8+T cells throughout the first year after HSCT in 18 patients using streptamer technology. A broad panel of promising LAAs was selected: Wilms tumor protein, proteinase 3, receptor for hyaluronan acid-mediated motility, apoptosis regulator Bcl-2, survivin, nucleophosmin, and fibromodulin. T cells specifically directed against AML- or CLL-associated antigens were found at very low frequencies in peripheral blood. Substantial frequencies of LAA-specific T cells could not be measured at any time point by flow cytometry. In contrast, abundant CMV-pp65-specific T cells were detected in CMV-seropositive patient-recipient pairs and an increase prompted by CMV infection could be demonstrated. In conclusion, T lymphocytes with specificities for the aforementioned LAAs can only be detected in minimal quantities in the early phase after allogeneic HSCT.
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany. Electronic address: Elke.Ruecker-Braun@uniklinikum-dresden.de.
authors.forename: Elke
authors.initials: E
authors.lastname: Rücker-Braun
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany; Deutsche Forschungsgemeinschaft Research Center for Regenerative Therapies Dresden, Medical Faculty, TU Dresden, Dresden, Germany.
authors.forename: Cornelia S
authors.initials: CS
authors.lastname: Link
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Schmiedgen
authors.affiliation: Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Tunger
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Vizjak
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Teipel
authors.affiliation: Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany; National Center for Tumor Diseases, University Hospital Carl Gustav Carus, TU Dresden, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.affiliation: Deutsche Forschungsgemeinschaft Research Center for Regenerative Therapies Dresden, Medical Faculty, TU Dresden, Dresden, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Kühn
authors.affiliation: Deutsche Forschungsgemeinschaft Research Center for Regenerative Therapies Dresden, Medical Faculty, TU Dresden, Dresden, Germany.
authors.forename: Yannik F
authors.initials: YF
authors.lastname: Fuchs
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Oelschlägel
authors.affiliation: Juno Therapeutics GmbH, Göttingen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Germeroth
authors.affiliation: Deutsche Forschungsgemeinschaft Research Center for Regenerative Therapies Dresden, Medical Faculty, TU Dresden, Dresden, Germany; Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany; National Center for Tumor Diseases, University Hospital Carl Gustav Carus, TU Dresden, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany; Deutsche Forschungsgemeinschaft Research Center for Regenerative Therapies Dresden, Medical Faculty, TU Dresden, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany; DKMS, German Bone Marrow Donor Center, Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: Medical Clinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Heidenreich
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D014408:Biomarkers, Tumor; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa