Fax: (713) 792-4296
Article first published online: 24 FEB 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 17, pages 3999–4008, 1 September 2011
How to Cite
Lee, B.-N., Gao, H., Cohen, E. N., Badoux, X., Wierda, W. G., Estrov, Z., Faderl, S. H., Keating, M. J., Ferrajoli, A. and Reuben, J. M. (2011), Treatment with lenalidomide modulates T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia. Cancer, 117: 3999–4008. doi: 10.1002/cncr.25983
Bang-Ning Lee, Alessandra Ferrajoli, and James M. Reuben conceived of design for the immunology studies and are responsible for preparation of the manuscript. Hui Gao and Evan N. Cohen were responsible for quantifying the T-cell subsets and TR cells, the functional studies of TCR-activated PBMC assays, and statistical analysis. Xavier Badoux, William G. Wierda, Zeev Estrov, Stefan H. Faderl, Alessandra Ferrajoli, and Michael J. Keating conceived and conducted the clinical trial, obtained informed consent from the patients, and reviewed the manuscript.
The authors acknowledge Maude Veech and Diane Hackett for their help in editing the manuscript, and Sanda Tin, Ying-Dong Li, and Matthew Galland for processing the blood samples for functional studies.
- Issue published online: 19 AUG 2011
- Article first published online: 24 FEB 2011
- Manuscript Accepted: 16 DEC 2010
- Manuscript Revised: 1 DEC 2010
- Manuscript Received: 23 AUG 2010
- chronic lymphocytic leukemia;
- immunomodulatory agents;
- T cells;
Lenalidomide, an immunomodulatory agent, has activity in lymphoproliferative disorders. The authors, therefore, evaluated its effects on T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia (CLL).
To study the immunomodulatory effects of lenalidomide in CLL, the authors recruited 24 patients with untreated CLL enrolled in a phase 2 clinical trial of lenalidomide and obtained peripheral blood specimens for immunologic studies consisting of enumeration of T cells and assessing their ability to synthesize cytokines after activation through T-cell receptor (TCR).
After 3 cycles of therapy, patients had a significant reduction in percentage (%) and absolute lymphocyte count (ALC) and an increase in percentage of T cells, percentage of activated CD8+ T cells producing IFN-γ, and percentage of regulatory T (TR) cells when compared with their respective levels before treatment. After 15 cycles of treatment, responder patients had significant reduction in percentage of lymphocytes and ALC, percentage of activated CD4+ T cells producing IL-2, IFN-γ, or TNF-α, and percentage of TR cells when compared with their perspective levels after 3 cycles of treatment. Furthermore, the numbers of activated CD4+ T cells producing IL-2, IFN-γ, or TNF-α, activated CD8+ T cells producing IFN-γ, and TR cells normalized to the range of healthy subjects.
Treatment with lenalidomide resulted in the normalization of functional T-cell subsets in responders, suggesting that lenalidomide may modulate cell-mediated immunity in patients with CLL. Cancer 2011;. © 2011 American Cancer Society.