Cited by 590Immunotherapy and Immune ResponsesImmune cells in cancerT-cell and B-cell Immunology

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Inhibition of the Differentiation of Dendritic Cells From CD34+ Progenitors by Tumor Cells: Role of Interleukin-6 and Macrophage Colony-Stimulating Factor

Menetrier-Caux, C., Montmain, G., Dieu, M.C., Bain, C., Favrot, M.C., Caux, C., Blay, J.Y.·1998·Blood

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Abstract

The escape of malignant cells from the immune response against the tumor may result from a defective differentiation or function of professional antigen-presenting cells (APC), ie, dendritic cells (DC). To test this hypothesis, the effect of human renal cell carcinoma cell lines (RCC) on the development of DC from CD34(+) progenitors was investigated in vitro. RCC cell lines were found to release soluble factors that inhibit the differentiation of CD34(+) cells into DC and trigger their commitment towards monocytic cells (CD14(+)CD64(+)CD1a-CD86(-)CD80(-)HLA-D Rlow) with a potent phagocytic capacity but lacking APC function. RCC CM were found to act on the two distinct subpopulations emerging in the culture at day 6 ([CD14(+)CD1a-] and [CD14(-)CD1a+]) by inhibiting the differentiation into DC of [CD14(+)CD1a-] precursors and blocking the acquisition of APC function of the [CD14(-)CD1a+] derived DC. Interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) were found to be responsible for this phenomenon: antibodies against IL-6 and M-CSF abrogated the inhibitory effects of RCC CM; and recombinant IL-6 and/or M-CSF inhibited the differentiation of DC similarly to RCC CM. The inhibition of DC differentiation by RCC CM was preceeded by an induction of M-CSF receptor (M-CSFR; CD115) and a loss of granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR; CD116) expression at the surface of CD34(+) cells, two phenomenon reversed by anti-IL-6/IL-6R and anti-M-C…

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Authors: Menetrier-Caux, C., Montmain, G., Dieu, M. C., Bain, C., Favrot, M. C., Caux, C., & Blay, J. Y.
Affiliations: From Unité Cytokine et Cancer, Unité INSERM 453, Centre Léon Bérard, Lyon, France; and Schering Plough, Dardilly, France.
Inserm (FR)
ORCID: Caux, C.
Blay, J.Y.
Venue: Blood
Publisher: American Society of Hematology
Published: 1998-12-15
Volume: 92
Issue: 12
Pages: 4778-4791
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood.v92.12.4778
OpenAlex: W193748226
Cited by: 590
References: 48
Citations by year: 2026: 3 · 2025: 4 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 9 · 2020: 20 · 2019: 16 · 2018: 13 · 2017: 9 · 2016: 25 · 2015: 26 · 2014: 19 · 2013: 30 · 2012: 25
FWCI: 6.33
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: dendritic cell differentiation, CD34+ progenitors, renal cell carcinoma, tumor immune evasion, interleukin-6, macrophage colony-stimulating factor, M-CSF receptor, GM-CSF receptor, antigen-presenting cells, monocyte differentiation, CD1a, CD14, soluble factors
MeSH terms: Antibodies, Carcinoma, Renal Cell, Cell Differentiation, Cell Division, Dendritic Cells, Dose-Response Relationship, Drug, Gene Expression Regulation, Humans, Lymphokines, Tumor Cells, Cultured, Interleukin-6, Immunophenotyping, Macrophage Colony-Stimulating Factor, Receptor, Macrophage Colony-Stimulating Factor, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Endothelial Growth Factors, Culture Media, Conditioned, Antigens, CD34, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Cell Size

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Inhibition of the Differentiation of Dendritic Cells From CD34+ Progenitors by Tumor Cells: Role of Interleukin-6 and Macrophage Colony-Stimulating Factor

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