title: Selective expansion of regulatory T cells during lenalidomide treatment of myelodysplastic syndrome with isolated deletion 5q.
abstract: Lenalidomide (LEN) leads to erythroid improvement in the majority of patients with myelodysplastic syndrome and isolated deletion of the long arm of chromosome 5 (MDS-del(5q)). This effect is believed to be exerted via its immunomodulatory properties, although the precise nature is still incompletely understood. We prospectively performed immune profiling in the bone marrow and blood of MDS-del(5q) patients undergoing LEN therapy for a median of 6 cycles. Therapy with LEN led to a significant increase in the median absolute lymphocyte count (1.3-fold, p = 0.013) without changes in the distribution of the T helper cells within the entire compartment. In parallel, the frequency of Treg increased significantly during treatment both in the peripheral blood (5.0 vs. 9.6 %, p = 0.001) and bone marrow (3.4 vs. 8.1 %, p = 0.001). Surprisingly, LEN treatment led to a decrease in TGFbeta levels, both in the peripheral blood (4.9 vs. 2.3 ng/ml, p = 0.039) and bone marrow (4.5 vs. 0.8 ng/ml, p = 0.023). These changes were not associated with an increase in pro-inflammatory Th17 cells. Taken together, our results demonstrate that LEN induces a shift in lymphocytic populations towards immunosuppression in MDS-del(5q) patients.
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Ekaterina
authors: E
authors: Balaian
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Claudia
authors: C
authors: Schuster
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Claudia
authors: C
authors: Schönefeldt
authors: Klinik für Hämatologie, Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
authors: Ulrich
authors: U
authors: Germing
authors: Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin Göttingen, Georg-August-Universität, Robert-Koch-Straße, 40, 37075, Göttingen, Germany.
authors: Detlef
authors: D
authors: Haase
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Sebastian
authors: S
authors: Tuve
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Rainer
authors: R
authors: Ordemann
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Gerhard
authors: G
authors: Ehninger
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Martin
authors: M
authors: Bornhäuser
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Uta
authors: U
authors: Oelschlaegel
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Brigitte
authors: B
authors: Mohr
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Malte
authors: M
authors: von Bonin
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany. uwe.platzbecker@uniklinikum-dresden.de.
authors: Uwe
authors: U
authors: Platzbecker
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität, Fetscherstr, 74, 01307, Dresden, Germany.
authors: Martin
authors: M
authors: Wermke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000748:Anemia, Macrocytic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D007155:Immunologic Factors; D016212:Transforming Growth Factor beta; D013792:Thalidomide; D000077269:Lenalidomide
keywords: Lenalidomide; MDS; Regulatory T cells; del(5q)