title: Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients.
abstract: Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: A C
authors.initials: AC
authors.lastname: Chan
authors.forename: P
authors.initials: P
authors.lastname: Neeson
authors.forename: E
authors.initials: E
authors.lastname: Leeansyah
authors.forename: K
authors.initials: K
authors.lastname: Tainton
authors.forename: H
authors.initials: H
authors.lastname: Quach
authors.forename: H M
authors.initials: HM
authors.lastname: Prince
authors.forename: D I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: D
authors.initials: D
authors.lastname: Ritchie
authors.forename: S P
authors.initials: SP
authors.lastname: Berzins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017252:CD3 Complex / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D017252:CD3 Complex; D016207:Cytokines; D013792:Thalidomide; D000077269:Lenalidomide