Immune Response and Immunotherapy in Chronic Lymphocytic Leukemia

Huergo-Zapico, Leticia; González-Rodríguez, Ana Pilar; Contesti, Juan; Fernández-Guizán, Azahara; Huerta, Andrea Acebes; López‐Soto, Alejandro; González, Segundo

doi:10.5772/27086

Cited by 1 publication

(2 citation statements)

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“…It is also remarkable, but not unexpected, that lenalidomide had only a modest effect on promoting the antileukemic activity of NK cells against primary leukemia cells. In fact, leukemia cells express low levels of ligands of NK cell activating receptors, probably due to immune evasion mechanisms, being highly resistant to NK cell-mediated lysis [ 1 , 30 ]. To increase the cytotoxic activity against leukemia cells it is necessary to favor the recognition of leukemia cells by NK and NKT-like cells.…”

Section: Discussionmentioning

confidence: 99%

“…A therapeutic intervention is scarcely required in patients with indolent disease, whereas chemotherapy treatment is frequently required in patients with advanced stage disease. However, CLL is generally considered as an incurable disease and, consequently, the development of new therapeutic strategies is a key goal in this malignancy [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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Lenalidomide Induces Immunomodulation in Chronic Lymphocytic Leukemia and Enhances Antitumor Immune Responses Mediated by NK and CD4 T Cells

Acebes-Huerta

Huergo-Zapico

González-Rodríguez

et al. 2014

BioMed Research International

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Lenalidomide is an immunomodulatory drug with therapeutic activity in chronic lymphocytic leukemia (CLL). However, it has pleiotropic effects, and the mechanism of action responsible for its therapeutic activity has not been well defined yet. Herein, we show that lenalidomide treatment does not have an effect on the proliferation of leukemia cells, but it increases the proliferation of B cells from healthy donors. Lenalidomide did not exert a direct effect on the apoptosis of leukemia cells obtained from CLL patients, although it indirectly induced their apoptosis through the activation of nonmalignant immune cells. Thus, lenalidomide markedly increased the proliferation of NK and CD4 T cells. The effect of lenalidomide on NK cells was secondary to the induction of IL-2 production by CD4 T cells. Accordingly, depletion of T cells or blockade of IL-2 activity completely abrogated the proliferation of NK cells. Additionally, lenalidomide enhanced NK and NKT-like cell-mediated natural cytotoxicity against leukemia cells from CLL patients. Lenalidomide also upregulated CD20 expression on leukemia cells and, accordingly, it had a synergistic effect with rituximab on promoting antibody-dependent cell-mediated cytotoxicity against primary leukemia cells. Overall, these observations provide a support for combining lenalidomide with rituximab as a treatment in CLL.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%