Soluble CD14 is a novel monocyte-derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro and present at abnormally high levels in vivo

Seiffert, Martina; Schulz, Angela; Öhl, S.; Döhner, Hartmut; Stilgenbauer, Stephan; Lichter, Peter

doi:10.1182/blood-2010-05-284505

Cited by 62 publications

(62 citation statements)

References 35 publications

(33 reference statements)

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“…[51][52][53] Not surprisingly then, monocytes have been convincingly shown to support the growth of malignant lymphocytes in both T-and B-cell NHL. 26,54 The vast majority of DLBCL originate from either germinalcenter B cells (that is, GCB type) or from B cells with a geneexpression profile resembling activated B cells (that is, ABC type). Each DLBCL subtype may preferentially exploit a particular pathway during lymphomagenesis.…”

Section: Discussionmentioning

confidence: 99%

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

et al. 2011

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Despite the use of modern immunochemotherapy regimens, almost 50% of patients with diffuse large-B-cell lymphoma will relapse. Current prognostic models, including the International Prognostic Index, incorporate patient and tumor characteristics. In contrast, recent observations show that variables related to host adaptive immunity and the tumor microenvironment are significant prognostic variables in non-Hodgkin lymphoma. Therefore, we retrospectively examined the absolute monocyte and lymphocyte counts as prognostic variables in a cohort of 366 diffuse large-B-cell lymphoma patients who were treated between 1993 and 2007 and followed at a single institution. The absolute monocyte and lymphocyte counts in univariate analysis predicted progression-free and overall survival when analyzed as continuous and dichotomized variables. On multivariate analysis performed with factors included in the IPI, the absolute monocyte and lymphocyte counts remained independent predictors of progression-free and overall survival. Therefore, the absolute monocyte and lymphocyte counts were combined to generate a prognostic score that identified patients with an especially poor overall survival. This prognostic score was independent of the IPI and added to its ability to identify high-risk patients.

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Section: Discussionmentioning

confidence: 99%

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

et al. 2011

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“…Bioactivity of rhIL-15 was assessed by B leukemic cell-depletion assays in PBMCs (n = 35), in combination with anti-CD20 Abs. Because they spontaneously die at low, but not high, density (13,30), B cell cultures were performed at high concentrations (10 3 10 6 cells/ml) (29). Under these conditions, no significant effect of RTX-or GA101-induced B leukemic cell depletion was detected after 3 d of treatment (p = 0.08 for RTX, p = 0.07 for GA101, compared with day 0), but the effect of anti-CD20 mAbs was optimal after 7 d of treatment (p = 0.05 for RTX, p = 0.04 for GA101 compared with day 0; n = 10).…”

Section: Coactivity Of Rhil-15 and Anti-cd20 Abs In B Leukemic Cell Dmentioning

confidence: 99%

Recombinant Human IL-15 Trans-Presentation by B Leukemic Cells from Chronic Lymphocytic Leukemia Induces Autologous NK Cell Proliferation Leading to Improved Anti-CD20 Immunotherapy

Laprévotte

Voisin

Ysebaert

et al. 2013

The Journal of Immunology

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Recombinant human IL-15 (rhIL-15) is one of the most promising cytokines for antitumor immunotherapy. In physiology IL-15 trans-presentation by accessory cells leads to pleiotropic activities, including activation of immune cells, such as NK cells. NK cells are largely involved in Ab-dependent cellular cytotoxicity mediated by therapeutic mAbs, such as rituximab, in chronic lymphocytic leukemia (CLL). Nevertheless, in CLL, Ab-dependent cellular cytotoxicity is relatively impaired by the low E:T ratio (NK/B leukemic cells). Thus, any strategy leading to an increase in NK cell number and activation status can offer new strategies for CLL treatment. To this end, we evaluated the effect of rhIL-15 on autologous NK cell stimulation in CLL samples. We show that rhIL-15 induces NK cell activation and proliferation, leading to improved B leukemic cell depletion. This phenomenon is significantly increased in the presence of anti-CD20 mAbs. In addition, the greater effect of obinutuzumab versus rituximab suggests a cooperative role between rhIL-15 signaling and CD16 signaling in the induction of NK cell proliferation. Moreover, rhIL-15–induced proliferation of autologous NK cells is strictly dependent on their interaction with B leukemic cells, identified in this study as new accessory cells for rhIL-15 trans-presentation. Thus, rhIL-15 is able to promote NK cell–based activity in Ab immunotherapy of CLL.

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“…8 Real-time polymerase chain reaction (PCR) was conducted using an ABIPrism7900RT sequence detection system (Applied Biosystems, Foster City, CA) and SYBR green ROX mix as DNA intercalating dye. Calculation of efficiency and ratio to housekeeping genes was performed as described.…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

“…7 Recently, our group highlighted the importance of undifferentiated, peripheral blood-derived monocytes in the CLL microenvironment. 8,9 Lenalidomide is an immunomodulatory drug that is currently undergoing clinical trial as a treatment of different B-cell malignancies, including CLL. [10][11][12][13] Here, it is believed to act mainly via the microenvironment because lenalidomide shows no direct cytotoxicity for CLL cells.…”

Section: Introductionmentioning

confidence: 99%

Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary cocultures by altering the myeloid microenvironment

Schulz

Dürr

Zenz

et al. 2013

Blood

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Soluble CD14 is a novel monocyte-derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro and present at abnormally high levels in vivo

Cited by 62 publications

References 35 publications

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

Recombinant Human IL-15 Trans-Presentation by B Leukemic Cells from Chronic Lymphocytic Leukemia Induces Autologous NK Cell Proliferation Leading to Improved Anti-CD20 Immunotherapy

Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary cocultures by altering the myeloid microenvironment

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