Human Renal Cell Carcinoma Induces a Dendritic Cell Subset That Uses T-Cell Crosstalk for Tumor-Permissive Milieu Alterations

Figel, Ainhoa-M.; Brech, Dorothee; Prinz, Petra U.; Lettenmeyer, Ulrike K.; Eckl, Judith; Turqueti-Neves, Adriana; Mysliwietz, Josef; Anz, David; Rieth, Nicole; Muenchmeier, Niklas; Büchner, Alexander; Porubský, Štefan; Siegert, Sabine; Segerer, Stephan; Nelson, Peter J.; Noeßner, Elfriede

doi:10.1016/j.ajpath.2011.03.011

Cited by 41 publications

(77 citation statements)

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“…In kidney, DC-SIGN is a protein that labels activated myeloid DCs with high T cell stimulation capability. 20 By performing double immunostaining for DC-SIGN/BDCA-1 in kidney frozen samples, Woltman et al 8 confirmed the reliability of DC-SIGN as a marker of myeloid kidney DCs by showing that all DC-SIGN + cells expressed BDCA-1. In this report, we observed DC-SIGN staining in elongated cells with cytoplasmic protrusions that were mainly present in the interstitium.…”

Section: Discussionmentioning

confidence: 91%

“…18,19 In kidney biopsies, DC-SIGN + cells stain with other known kidney DC markers (BDCA-1, 8 HLA-DR, 8 CD68, 7,8 and CX3CR1 10 ), show an activated but not fully mature DC phenotype, and are associated with high T cell stimulation capability. 20 Our knowledge of the role of kidney DCs in human allografts is limited to three studies 8,9,21 (Table 1). These studies have shown that compared with the pretransplant baseline, rejecting allografts display increased number of DCs, which are associated with inflammation, atrophy, and subsequent allograft dysfunction.…”

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confidence: 99%

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Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

Batal

Serres

Safa

et al. 2015

Journal of the American Society of Nephrology

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Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

Batal

Serres

Safa

et al. 2015

Journal of the American Society of Nephrology

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“…Interestingly, these two types of DCs display different phenotypes and capacities of T-cell priming, presumably due to the distinctive microenvironments in which they develop. Isolated DCs display an immature phenotype (CD80 À , CD86 À , CD83 À , and HLA-DR À ) (Gigante et al, 2009;Giraldo et al, 2015), express tumor-promoting molecules (eg, TNF-α and MMP-9) (Figel et al, 2011), and induce a dysfunctional in vitro T-cell activation (Cabillic et al, 2006;Figel et al, 2011). On the other hand, DCs within immune aggregates exhibit a mature phenotype and express activation markers Middel, Brauneck, Meyer, & Radzun, 2010;Troy et al, 1998) (Fig.…”

Section: The Ccrcc Tumor Microenvironmentmentioning

confidence: 98%

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Becht¹,

Giraldo²,

Germain³

et al. 2016

Advances in Immunology

172

132

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“…CD14 is a specific monocyte/macrophage marker, although it can also be found on subsets of dendritic cells. 26 CD33 is expressed on non-terminally differentiated myeloid cells 27 and CD163 is linked to macrophage anti-inflammatory functions. [28][29][30] The cellular distribution of these myeloid cell populations in tumor epithelium and stroma is depicted in Table 2C.…”

Section: Infiltration Of Myeloid Cell Populationsmentioning

confidence: 99%

“…26 CD33 is expressed on non-terminally differentiated myeloid cells 27 and CD163 is linked to macrophage anti-inflammatory functions. [28][29][30] The cellular distribution of these myeloid cell populations in tumor epithelium and stroma is depicted in Table 2C. In general, tumors displayed a suppressive microenvironment as indicated by the high numbers of CD163-positive cells present.…”

Section: Infiltration Of Myeloid Cell Populationsmentioning

confidence: 99%

Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer

et al. 2014

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y These authors contributed equally to this study.Keywords: epithelial ovarian cancer, IL-6, interleukin-6; IL-6R, interleukin-6 receptor, pSTAT3, tumor-infiltrating myeloid cells Abbreviations: DSS, disease-specific survival; EOC, epithelial ovarian cancer; IL-6R, interleukin-6, IL-6, interleukin-6 receptor; FIGO, International Federation of Gynecology and Obstetrics; MDSC, myeloid-derived suppressor cell; pSTAT3, phosphorylated signal transducer and activator of transcription 3; T reg, regulatory T cell; TMA, tissue microarray; TAM, tumor-associated macrophage; TIL, tumor-infiltrating lymphocytes; TIM, tumor-infiltrating myeloid cellAn increased level of interleukin-6 (IL-6) in epithelial ovarian cancer (EOC) is correlated with a worse prognosis. IL-6 stimulates tumor-growth and inflammation. We investigated the intricate interaction between the IL-6 signaling pathway and tumor-infiltrating myeloid cells (TIMs) to determine their prognostic impact in EOC. 160 EOC samples were analyzed for the expression of IL-6, its receptor (IL-6R) and downstream signaling via pSTAT3 by immunohistochemistry. Triple color immunofluorescence confocal microscopy was used to identify myeloid cell populations by CD14, CD33, and CD163. The relationship between these markers, tumor-infiltrating immune cells, clinical-pathological characteristics and survival was investigated. EOC displayed a dense infiltration with myeloid cells, in particular of the CD163 C type. The distribution pattern of all myeloid subtypes was comparable among the different histological subtypes. Analysis of the tumor cells revealed a high expression of IL-6R in 15% and of IL-6 in 23% of patients. Interestingly, tumors expressing IL-6 or IL-6R formed two different groups. Tumors with a high expression of IL-6R displayed low mature myeloid cell infiltration and a longer disease-specific survival (DSS), especially in late stage tumors. High expression of IL-6R was an independent prognostic factor for survival by multivariate analyses (hazard ratio D 0.474, p D 0.011). In contrast, tumors with high epithelial IL-6 expression displayed a dense infiltration of mature myeloid cells and were correlated with a shorter DSS. Furthermore, in densely CD8 C T-cell infiltrated tumors, the ratio between these lymphoid cells and CD163 C myeloid cells was predictive for survival. Thus, IL-6 and IL-6R are opposite markers for myeloid cell infiltration and survival.

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Human Renal Cell Carcinoma Induces a Dendritic Cell Subset That Uses T-Cell Crosstalk for Tumor-Permissive Milieu Alterations

Abstract: The mononuclear infiltrate in renal cell carcinoma (RCC) has been associated with the immunogenic nature of this tumor type and the clinical response rates achieved with immunotherapy.

Cited by 41 publications

References 61 publications

Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer

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