Cancer · 2011
Treatment with lenalidomide modulates T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia.
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Lee Bang-Ning, Gao Hui, Cohen Evan N, Badoux Xavier, Wierda William G, Estrov Zeev, Faderl Stefan H, Keating Michael J, Ferrajoli Alessandra, Reuben James M
Аннотация
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-γ, 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-γ, or TNF-α, 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-γ, or TNF-α, activated CD8(+) T cells producing IFN-γ, 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.
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-γ, 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-γ, or TNF-α, 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-γ, or TNF-α, activated CD8(+) T cells producing IFN-γ, 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.