Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells

Zou, Weiping; Machelon, Véronique; Coulomb-L'Hermin, Aurore; Borvak, Jozef; Nomé, Françoise; Isaeva, Tatyana; Wei, Shuang; Krzysiek, Roman; Durand-Gasselin, Ingrid; Gordon, Alan N.; Pustilnik, Terri B.; Curiel, David T.; Galanaud, Pierre; Capron, Frédérique; Émilie, Dominique; Curiel, Tyler J.

doi:10.1038/nm1201-1339

Cited by 588 publications

(561 citation statements)

References 42 publications

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“…Extracellular HMGB1 mediates endotoxin lethality and inflammation [32,[42][43][44][45][46]. These findings suggest that HMGB1 may be involved in regulating the function of PDC, which have been implicated in the pathogenesis of cancer [47,48] and chronic inflammatory conditions like systemic lupus erythematosus and allergy [49][50][51].…”

Section: Introductionmentioning

confidence: 89%

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

et al. 2005

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Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the bestcharacterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases. IntroductionDendritic cells (DC) are potent antigen-presenting cells bridging the innate and adaptive immune responses. To date, two subsets of DC have been identified in humans: myeloid DC and plasmacytoid DC (PDC), the latter also referred to as type I interferon (IFN-a)-producing cells [1][2][3][4][5][6]. PDC recognize viral or bacterial DNA patterns, consisting of unmethylated CpG motifs in the context of species-dependent surrounding sequences (CpG) [7]. As a consequence they produce, within a few hours, large amounts of . Based on their ability to induce IFN-a secretion by PDC, two types of CpG have been described: CpG 2216 (CpG-A), which induces high amounts of IFN-a, and CpG 2006 (CpG-B), which promotes survival, maturation and migration of PDC to the lymph nodes, but induces lower amounts of . PDC sustain the priming of naive T cells and their differentiation into Th1/Th2 effectors [15][16][17] or into regulatory T cells [16,[18][19][20][21][22].Recent studies shed light on the events involved in the recognition of microbial DNA by human PDC, the only subset of human DC that expresses the Toll-like receptor 9 (TLR9) [12]. Both CpG-A and CpG-B have been shown to activate PDC via TLR9 [23]. Upon phagocytosis PDC lyse microorganisms in phagolysosomes, where microbial DNA interacts with and activates TLR9 derived from the endoplasmic reticulum [24]. TLR9 activation leads to recruitment of the MyD88 adaptor protein and phosphorylation of the IL-1R-associated kinase (IRAK). Phosphorylated IRAK associates with the adaptor molecule TNF-associated factor 6 (TRAF6) [25]. Two separate signaling pathways, JNK and NF-jB, are then activated, promoting PDC maturation and survival. IFN-a induction, an event exclusively occurring in PDC, depends on the formation of a complex consisting of MyD88, TRAF6 and the IRF7 transcription factor, as well as on TRAF6-dependent ubiquitination [26].The events that determine the outcome of the interaction of PDC with T cells, and in particular the induction of effector or regulatory immune responses, are poorly characterized. Environmental signals that Here we report that HMGB1 is exported from the nucleus of PDC upon selective engagement of TLR9 an...

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Section: Introductionmentioning

confidence: 89%

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

et al. 2005

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“…The relevance of PDCs in cancer immunosurveillance has been recently shown in mice [68,69], where TLR9-activated PDCs lead to the regression of subcutaneous B16 melanoma tumors, by orchestrating the sequential activation of NK cells, MDCs and CD8 + T cells. The characterization of PDCs has been performed in a variety of human neoplasms [54,[70][71][72]. However, the potential impact of PDCs for cancer immunity is based largely on in vitro studies of circulating PDCs, while PDCs detectable at the tumour site (tumor-associated PDCs, TAPDCs) are poorly characterized.…”

Section: Reviewmentioning

confidence: 99%

Trafficking properties of plasmacytoid dendritic cells in health and disease

Sozzani

Vermi

Prete

et al. 2010

Trends in Immunology

146

151

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“…Depending on the cytokine milieu encountered in tumors, DCs can either mediate anti-tumor activity or support tumor growth and metastasis. In fact, increasing evidence from analyses of human ovarian, breast, prostate and renal cell carcinoma reveals the presence of tumor-promoting rather than tumor-suppressing dendritic cells, and altered dendritic cell function and differentiation is likely to be one of the most fundamental mechanisms by which tumors escape immune responses [231][232][233][234][235]. Pro-tumorigenic dendritic cells can favor metastasis by inducing tumor immunotolerance and by promoting tumor angiogenesis.…”

Section: Nks and Dcsmentioning

confidence: 99%

“…Tumor cells, TAMs and tumoral immunosuppressive T cells can secrete high amounts of VEGF-A, IL-6, macrophage colony-stimulating factor (M-CSF), COX2, IL-10, TGFb and gangliosides, which suppress maturation of DCs [192]. Most myeloid DCs found in human ovarian, breast, prostate and renal cell carcinoma are therefore immature and may induce tumor immunotolerance [231][232][233][234]. Tumor-secreted IL-10 and VEGF also induce expression of B7-H1 on myeloid dendritic cells, a ligand for PD-1 receptor expressed on suppressor T cells [238].…”

Section: Nks and Dcsmentioning

confidence: 99%

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Kopfstein

Christofori

2006

Cell. Mol. Life Sci.

209

160

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Abstract. The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix Cell. Mol. Life Sci. 63 (2006) 449-468 1420-682X/06/040449-20 DOI 10.1007/s00018-005-5296-8 © Birkhäuser Verlag, Basel, 2006 adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic process.

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Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells

Cited by 588 publications

References 42 publications

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Trafficking properties of plasmacytoid dendritic cells in health and disease

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

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