Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

• Published in: Leukemia Vol. 24; no. 3; pp. 592 - 600
• Main Authors: Chan, A C, Neeson, P, Leeansyah, E, Tainton, K, Quach, H, Prince, H M, Godfrey, D I, Ritchie, D, Berzins, S P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2010; Nature Publishing Group
• Subjects: 631/250/1619/554/383; 692/699/67/1990/1673; 692/700/565/1436; Acute myeloid leukemia; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Blood; Bone marrow; Cancer; Cancer Research; CD3 Complex - analysis; Cell proliferation; Critical Care Medicine; Cytokines; Cytokines - biosynthesis; Drug therapy; Female; Health aspects; Health sciences; Health services; Hematologic and hematopoietic diseases; Hematology; Hematopoiesis; Humans; Hypotheses; Immune response; Immunology; Immunotherapy; Intensive; Internal Medicine; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Longitudinal Studies; Lymphocytes T; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - immunology; Natural killer cells; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Oncology; original-article; Patient outcomes; Patients; Physiological aspects; Stem cells; T cells; Targeted cancer therapy; Thalidomide - analogs & derivatives; Thalidomide - pharmacology; Thalidomide - therapeutic use; Australia; United States > US; Victoria Australia; myelodysplastic syndrome; NKT cells; lenalidomide; Antineoplastic agent; Human; Treatment; Natural killer T cell; Hematology; Lenalidomide; Malignant hemopathy; Medical screening; Myelodysplastic syndrome; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.279

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.