Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines

Bakdash, Ghaith; Buschow, Sonja I.; Gorris, Mark A.J.; Halilović, Altuna; Hato, Stanleyson V.; Sköld, Annette E.; Sittig, Simone P.; Torensma, Ruurd; Boer, Tjitske Duiveman-de; Schröder, Christoph; Smits, Evelien; Figdor, Carl G.; Vries, I. Jolanda M. de

doi:10.1158/0008-5472.can-15-1695

Cited by 93 publications

(126 citation statements)

References 52 publications

(35 reference statements)

Supporting

Mentioning

121

Contrasting

Order By: Relevance

“…In vitro , human cDC2 are potent in the activation of Th1, Th2, Th17 and CD8 + T cells, suggesting the capacity to promote a wide range of immune responses in vivo . Subsets of cDC2 defined by CD5 and other markers differ in their production of TNF‐ α , IL‐6, IL‐10 and IL‐23 in response to TLR ligation . CD5‐high ‘DC‐like’ cDC2 are more active in CCR7‐dependent migration, stimulate high naive T‐cell proliferation and preferential priming of Th2, Th17, Th22 and regulatory T cells.…”

Section: Irf4/klf4/notch2‐dependent Myeloid Cdc2mentioning

confidence: 99%

“…8,9 CD14 + CD1c + cells have previously been detected and characterized as CD1c + monocytes 139 but by gene expression, most cluster with cDC2. 8,9 In tissues, especially during inflammation, and in humans affected by cancer, it is relatively easy to detect dual positive CD1c + CD14 + cells 12,13,140 but the origin of these may be difficult to ascertain precisely because as mo-DC, they converge towards the monocyte-like cDC2 phenotype. 30,141 Antibodies to CD2, CD5, FceR1, CLEC4A (DCIR/CD367) and CLEC10A (CD301) may be useful but are still inducible and labile in inflammation.…”

Section: Irf4/klf4/notch2-dependent Myeloid Cdc2mentioning

confidence: 99%

“…Subsets of cDC2 defined by CD5 and other markers differ in their production of TNF-a, IL-6, IL-10 and IL-23 in response to TLR ligation. 8,140 CD5-high 'DC-like' cDC2 are more active in CCR7-dependent migration, stimulate high naive T-cell proliferation and preferential priming of Th2, Th17, Th22 and regulatory T cells. 'Monocyte-like' cDC2 with lower CD5 are less active in proliferation assays and produce mainly Th1 cells.…”

Section: Functions and Role In Immunitymentioning

confidence: 99%

See 2 more Smart Citations

Human dendritic cell subsets: an update

2018

View full text Add to dashboard Cite

SummaryDendritic cells (DC) are a class of bone‐marrow‐derived cells arising from lympho‐myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU.1, ID2, E2‐2, ZEB2, KLF4, IKZF1 and BATF3. DC haematopoiesis is conserved between mammalian species and is distinct from monocyte development. Although monocytes can differentiate into DC, especially during inflammation, most quiescent tissues contain significant resident populations of DC lineage cells. An extended range of surface markers facilitates the identification of specific DC subsets although it remains difficult to dissociate cDC2 from monocyte‐derived DC in some settings. Recent studies based on an increasing level of resolution of phenotype and gene expression have identified pre‐DC in human blood and heterogeneity among cDC2. These advances facilitate the integration of mouse and human immunology, support efforts to unravel human DC function in vivo and continue to present new translational opportunities to medicine.

show abstract

Section: Irf4/klf4/notch2‐dependent Myeloid Cdc2mentioning

confidence: 99%

Section: Irf4/klf4/notch2-dependent Myeloid Cdc2mentioning

confidence: 99%

Section: Functions and Role In Immunitymentioning

confidence: 99%

See 1 more Smart Citation

Human dendritic cell subsets: an update

2018

View full text Add to dashboard Cite

show abstract

“…Furthermore, they are often outnumbered by other myeloid cell subsets, such as tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) that actively suppress the immune system [23][24][25] . Moreover, we and others have recently described the enrichment of a myeloid cell population in cancer patients that co-expresses markers of monocytes/TAMs (such as CD14, CD163) and cDC2s (CD1c) [26][27][28] . Given their phenotypic distinction from monocytes and macrophages, these cells are called 'CD14 + DCs' 27 .…”

Section: Introductionmentioning

confidence: 90%

“…Given their phenotypic distinction from monocytes and macrophages, these cells are called 'CD14 + DCs' 27 . CD14 + DCs are increased in the circulation of advance stage cancer patients and infiltrate both primary and metastatic tumour sites [26][27][28] . How these CD14 + DCs are generated remains yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture

Blasio

Tazzari

Wigcheren

et al. 2019

Preprint

View full text Add to dashboard Cite

The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light into multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We developed a novel human, organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multi-cellular tissue architecture. By co-culturing keratinocytes, fibroblasts and immune cells with melanoma cells, onto a de-cellularized dermis, we generated a reconstructed TME that closely recapitulates tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC we observed the tumour-driven conversion of cDC2s into CD14 + DCs, characterized by a an immunosuppressive phenotype. The OMC provides a valuable complement to current approaches to study the TME.

show abstract

Human Dendritic Cell Enrichment and Their Activation of T Cells

Lubin,

Gvili,

Hazan

et al. 2023

Current Protocols

View full text Add to dashboard Cite

Dendritic cells (DCs) enable the immune system to mount and modulate precisely targeted responses to various threats across the organism by bridging innate and adaptive immunity. Historically, DCs have been classified as conventional (cDC) and plasmacytoid (pDC). More recently, cDCs were acknowledged as a heterogenous population composed of several subsets. Examining the functional diversity of cDCs in healthy homeostasis and pathology requires a robust experimental pipeline, beginning with an efficient enrichment protocol in preparation for cell sorting. Unfortunately, several commercial DC enrichment kits were developed before the discovery of the more recently described DC populations. Here, we detail two approaches to enrich human blood DCs or certain DC subsets and an in vitro protocol to examine DC stimulation of naïve T cells. The methods employed here overcome many hurdles encountered while enriching human DC subsets. Basic Protocol 1 describes a method that will enrich pDC, Axl Siglec6‐DC (AS‐DC), cDC1, DC2, DC3, monocytes, and human HLA+ cells by crosslinking unwanted cells to erythrocytes. Basic Protocol 2 describes the enrichment of pDC, AS‐DC, cDC1, and DC2 but not DC3 via a highly efficient negative magnetic selection that is valuable in circumstances where DC3 is not required. Finally, Basic Protocol 3 describes a conventional protocol to perform a Mixed leucocyte Reaction (MLR) following the isolation of these DC subsets. These methods detail the advantages and pitfalls when isolating a heterogeneous population of cells. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Human peripheral mononuclear phagocyte enrichmentBasic Protocol 2: DC enrichment of pDC, cDC1, AS‐DC, and DC2 but not DC3Basic Protocol 3: Basic mixed lymphocyte reaction protocol with sorted human DC subsets

show abstract

Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines

Cited by 93 publications

References 52 publications

Human dendritic cell subsets: an update

Human dendritic cell subsets: an update

The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture

Human Dendritic Cell Enrichment and Their Activation of T Cells

Contact Info

Product

Resources

About