Treatment with lenalidomide modulates T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia.
Author(s): Lee BN, Gao H, Cohen EN, Badoux X, Wierda WG, Estrov Z, Faderl SH, Keating MJ, Ferrajoli A, Reuben JM
Affiliation(s): Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Publication date & source: 2011-09-01, Cancer., 117(17):3999-4008. Epub 2011 Feb 24.
Publication type: Research Support, Non-U.S. Gov't
BACKGROUND: 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). METHODS: 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). RESULTS: 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-gamma, and percentage of regulatory T (T(R) ) 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-gamma, or TNF-alpha, and percentage of T(R) cells when compared with their perspective levels after 3 cycles of treatment. Furthermore, the numbers of activated CD4(+) T cells producing IL-2, IFN-gamma, or TNF-alpha, activated CD8(+) T cells producing IFN-gamma, and T(R) cells normalized to the range of healthy subjects. CONCLUSIONS: 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 (c) 2011 American Cancer Society.