Elevated Interleukin-6 and G-CSF in Human Pancreatic Cancer Cell Conditioned Medium Suppress Dendritic Cell Differentiation and Activation

Bharadwaj, Uddalak; Li, Min; Zhang, Rongxin; Chen, Changyi; Yao, Qizhi

doi:10.1158/0008-5472.can-06-3963

Cited by 134 publications

(100 citation statements)

References 45 publications

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“…These factors are highly expressed in RCC 5,48 and may thus promote the differentiation of ercDCs in situ. The identification of these factors was based on a study design that was distinct from those reported by others 37,49,50 : cultivation supplements, IL-4, or GM-CSF, which are commonly used to differentiate DCs in vitro but do not represent a DC differentiation pathway in vivo, 12 were deliberately omitted. Thus, we believe that the used cultivation system better reflected the natural process of monocyte differentiation when entering the tissue milieu.…”

Section: Discussionmentioning

confidence: 99%

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

Figel

Brech

Prinz

et al. 2011

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 99%

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

Figel

Brech

Prinz

et al. 2011

The American Journal of Pathology

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“…While promoting macrophage enrichment, pancreatic cancer cells have been shown to inhibit dendritic cells differentiation via secretion of IL-6 and G-CSF 36 .…”

Section: Tumour-educated Macrophages and Hyperglycaemia Promote Invasmentioning

confidence: 99%

Tumour‐educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion

2014

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Tumour-educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion.Karnevi, Emelie; Andersson, Roland; Rosendahl, Ann Link to publication Citation for published version (APA): Karnevi, E., Andersson, R., & Rosendahl, A. (2014). Tumour-educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion. Immunology and Cell Biology, 92(6), 543-552. DOI: 10.1038/icb.2014.22 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal High glucose conditions further enhanced the tumour-driven macrophage enrichment and associated IL-6 and IL-8 cytokine levels. In addition, hyperglycaemia enhanced the responsiveness of tumour-educated macrophages to lipopolysaccharide, with elevated cytokine secretion compared to normal glucose levels. Tumour-educated macrophages were found to promote pancreatic cancer cell invasion in vitro, which was significantly enhanced at high glucose. The anti-diabetic drug metformin shifted the macrophage phenotype polarization and reduced the tumour cell invasion at normal, but not high, glucose levels. In conclusion, this study demonstrates that pancreatic cancer cells stimulate differentiation of macrophages with pro-tumour properties that are further enhanced by hyperglycaemia. These findings highlight important crosstalk between tumour cells and TAMs in the local tumour microenvironment that may contribute to disease progression in pancreatic cancer patients with hyperglycaemia and T2D.

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“…They found that one of the soluble factors released by pancreatic cancer cells and being responsible for inhibiting DC differentiation and activation is IL-6; more recently, Tjomsland et al (64) evidenced the implication of the inflammatory factor PGE 2 in patients with ductal pancreatic adenocarninoma, causing semimature blood DC. Thus, the immunosuppressive microenvironment created by tumors themselves through the release of soluble factors renders DC tolerant (63)(64)(65). At present, we do not know whether IL-8-and IL-6-secreting (but not IL-10) pBSDL-J28 mature MoDC could be generated in vivo and take part in the suppressor environment within tumoral and inflammatory pancreas.…”

Section: Discussionmentioning

confidence: 96%

A Novel Tumor-Associated Pancreatic Glycoprotein Is Internalized by Human Dendritic Cells and Induces Their Maturation

Franceschi

Collignon

Isnardon

et al. 2011

The Journal of Immunology

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Aberrant glycosylation or overexpression of cell-surface glycosylated tumor-associated Ags (TAA) distinguish neoplastic from normal cells. Interactions of TAA MUC1 and HER2/neu with dendritic cells (DC) preclude efficient processing, which impairs immune responses. It is thus important to define the mechanisms of interactions between DC and glycosylated TAA and their trafficking and processing for further T cell activation. In this work, we study interactions between DC and the oncofetal fucose-rich glycovariants of bile salt-dependent lipase (BSDL), expressed in pancreatic cancer tissues and referred to as pathological BSDL carrying the fucosylated J28 glycotope (pBSDL-J28) because it is characterized by the mAb J28. The expression of pBSDL-J28 was assessed by immunohistochemistry and quantified by confocal microscopy. Nontumoral pancreatic tissues and cells do not express pBSDL-J28. Using multidisciplinary approaches and functional studies, we provide the first evidence, to our knowledge, that this tumoral glycoprotein is rapidly internalized by human DC through macropinocytosis and endocytosis via mannose receptors and then transported to late endosomes for processing. Interestingly, pBSDL-J28 per se induced DC maturation with increased expression of costimulatory and CD83 molecules associated with cytokine secretion (IL-8 and IL-6). Surprisingly, DC retained their full ability to internalize Ags, making this maturation atypical. Finally, the allogeneic pBSDL-J28–treated DC stimulated lymphocyte proliferation. Besides, pulsing DC with pBSDL-J28 C-terminal glycopolypeptide and maturation with CD40L triggered CD4+ and CD8+ T cell proliferation. Therefore, interactions of pBSDL-J28, expressed on tumoral pancreatic tissue, with DC may lead to adequate Ag trafficking and processing and result in T cell activation.

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Elevated Interleukin-6 and G-CSF in Human Pancreatic Cancer Cell Conditioned Medium Suppress Dendritic Cell Differentiation and Activation

Cited by 134 publications

References 45 publications

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

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

Tumour‐educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion

A Novel Tumor-Associated Pancreatic Glycoprotein Is Internalized by Human Dendritic Cells and Induces Their Maturation

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