Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients

Valteau‐Couanet, Dominique; Leboulaire, Christophe; Maincent, Kim; Tournier, Muriel; Hartmann, Olivier; Bénard, Jean; Beaujean, F.; Boccaccio, C; Zitvogel, Laurence; Angevin, Eric

doi:10.1182/blood.v100.7.2554

Cited by 54 publications

(33 citation statements)

References 27 publications

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“…Supporting this hypothesis, our results indicate that mDC-dependent IFN-g production by NK cells is higher after IM therapy and dictates the clinical outcome under IM. mDC can indeed form active immunologic synapses with resting or preactivated NK cells through a mechanism involving cytokines and cell to cell contacts (13,28). It is conceivable that in addition to IM, other pathophysiologic conditions might deliver TLR4 ligands (such as HMGB1; ref.…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cell IFN-γ Levels Predict Long-term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor–Bearing Patients

et al. 2009

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Clinical outcomes of gastrointestinal stromal tumor (GIST)-bearing patients treated with imatinib mesylate (IM) are variable. Other than the site of mutation within the c-kit gene, prognostic features of GIST remain undefined. IM can exhibit off-target effects such as triggering natural killer (NK) cell activity. We addressed whether NK cell functions could predict long term survival with IM. NK cell functions were followed up in 77 GIST patients enrolled onto two phase III trials. ''Immunologic responders'' were defined as patients whose NK cell IFN-; values after 2 months of IM were higher than or equal to the baseline value at entry into the trial. The prognostic effect of IFN-; on progression-free survival was assessed by a Wald test in a Cox regression analysis using the landmark method and stratified by trial and on the c-kit mutational status. Fifty-six patients were evaluable for the NK cell IFN-; responses at baseline and 2 months. Their median follow-up for progression-free survival was 3.7 years. Thirtyfour of 56 patients were immunologic responders to IM. In the Cox regression analysis, immunologic responders possessed a hazard ratio of progression or death equal to 0.29 (95% confidence interval, 0.12-0.70; P = 0.006) compared with nonresponders. Kaplan-Meier 2-year survival estimates were 85% for immunologic responders and 50% for nonresponders. Moreover, the immunologic response added prognostic value to the c-kit mutation. The NK cell IFN-; production after 2 months of treatment could be considered an independent predictor of long term survival in advanced GISTs treated with

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Section: Discussionmentioning

confidence: 99%

Natural Killer Cell IFN-γ Levels Predict Long-term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor–Bearing Patients

et al. 2009

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“…NK/LAK cells were derived from the same mice or, when indicated, from RAG-1 knockout mice, kindly provided by P. Dellabona (Milano), using B cell-depleted splenocytes cultured for 3 days in medium containing 1 U/ll human rIL-2 (Chiron Corporation, Emeryville, CA) and propagated as described. 31 In selected experiment, CD31 lymphocytes were depleted by magnetic bead sorting, as described. 32 NK/LAK cells were routinely characterized by flow cytometry after staining with mAbs specific for NKG2A, NK1.1, Ly49A, CD94, CD3, H2-K b , IA b and appropriate PerCP, FITC-and PE-conjugated second step reagents (PharMingen, BD Bioscences, CA).…”

Section: Cellsmentioning

confidence: 99%

Melanoma cells interfere with the interaction of dendritic cells with NK/LAK cells

Capobianco

Rovere‐Querini

Rugarli

et al. 2006

Intl Journal of Cancer

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Dendritic cells (DCs) and natural killer (NK) cells are key players at the interface between innate resistance and acquired immunity. NK cells can induce DC maturation, a differentiation process whereby DCs respond to a environmental stimulus and acquire the ability of eliciting adaptive immunity. Conversely, maturing DCs promote NK functions in vivo and in vitro. This interplay has important consequences on the immune response to pathogens and possibly to neoplastic cells. Here, we show that B16 melanoma cells actively modulate the interaction between DCs derived from bone marrow precursors and NK/LAK cells propagated from the spleen of C57BL/6 mice. DCs increased in a dose-dependent manner the ability of NK/LAK cells to kill melanoma cells and to produce cytokines. This activatory cross-talk entailed the production of IL-18 by DCs and of IFN-c by NK/LAK cells. Melanoma cells were not a passive target of NK activity; they regulated the outcome of the interaction between DCs and NK/LAK cells, inhibiting the in vitro production of cytokines as effectively as the genetic deletion of IL-18 or IFN-c. Interference with the NK/DC interaction possibly represents a mechanism used by growing tumors to evade the immune response. ' 2006 Wiley-Liss, Inc.

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“…The enhancement of NK cell activity by collateral cells such as neutrophils, 37,38 monocytes, 39-41 macrophages, [42][43][44] and dendritic cells [45][46][47][48] has been well documented. Many of these myeloid cells express Gr-1.…”

Section: Immunodepletion Of Gr-1mentioning

confidence: 99%

Natural killer cells require monocytic Gr-1⁺/CD11b⁺myeloid cells to eradicate orthotopically engrafted glioma cells

et al. 2016

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Malignant gliomas are resistant to natural killer (NK) cell immune surveillance. However, the mechanisms used by these cancers to suppress antitumor NK cell activity remain poorly understood. We have recently reported on a novel mechanism of innate immune evasion characterized by the overexpression of the carbohydrate-binding protein galectin-1 by both mouse and rat malignant glioma. Here, we investigate the cytokine profile of galectin-1-deficient GL26 cells and describe the process by which these tumors are targeted by the early innate immune system in RAG1¡/¡ and C57BL/6J mice. Our data reveal that galectin-1 knockdown in GL26 cells heightens their inflammatory status leading to the rapid recruitment of Gr-1C myeloid cells and NK1.1 C NK cells into the brain tumor microenvironment, culminating in tumor clearance. We show that immunodepletion of Gr-1 C myeloid cells in RAG1 ¡/¡ mice permits the growth of galectin-1-deficient glioma despite the presence of NK cells, thus demonstrating an essential role for myeloid cells in the clearance of galectin-1-deficient glioma. Further characterization of tumor-infiltrating Gr-1C cells reveals that these cells also express CCR2 and Ly-6C, markers consistent with inflammatory monocytes. Our results demonstrate that Gr-1C myeloid cells, often referred to as myeloid-derived suppressor cells (MDSCs), are required for antitumor NK cell activity against galectin-1-deficient GL26 glioma. We conclude that glioma-derived galectin-1 represents an important factor in dictating the phenotypic behavior of monocytic Gr-1 C

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Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients

Cited by 54 publications

References 27 publications

Natural Killer Cell IFN-γ Levels Predict Long-term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor–Bearing Patients

Natural Killer Cell IFN-γ Levels Predict Long-term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor–Bearing Patients

Melanoma cells interfere with the interaction of dendritic cells with NK/LAK cells

Natural killer cells require monocytic Gr-1⁺/CD11b⁺myeloid cells to eradicate orthotopically engrafted glioma cells

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Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients

Cited by 54 publications

References 27 publications

Natural Killer Cell IFN-γ Levels Predict Long-term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor–Bearing Patients

Natural Killer Cell IFN-γ Levels Predict Long-term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor–Bearing Patients

Melanoma cells interfere with the interaction of dendritic cells with NK/LAK cells

Natural killer cells require monocytic Gr-1+/CD11b+myeloid cells to eradicate orthotopically engrafted glioma cells

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Natural killer cells require monocytic Gr-1⁺/CD11b⁺myeloid cells to eradicate orthotopically engrafted glioma cells