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Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?

BACKGROUND: Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most c...

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Autores principales: Tjomsland, Vegard, Sandström, Per, Spångeus, Anna, Messmer, Davorka, Emilsson, Johan, Falkmer, Ursula, Falkmer, Sture, Magnusson, Karl-Eric, Borch, Kurt, Larsson, Marie
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847547/
https://www.ncbi.nlm.nih.gov/pubmed/20214814
http://dx.doi.org/10.1186/1471-2407-10-87
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author Tjomsland, Vegard
Sandström, Per
Spångeus, Anna
Messmer, Davorka
Emilsson, Johan
Falkmer, Ursula
Falkmer, Sture
Magnusson, Karl-Eric
Borch, Kurt
Larsson, Marie
author_facet Tjomsland, Vegard
Sandström, Per
Spångeus, Anna
Messmer, Davorka
Emilsson, Johan
Falkmer, Ursula
Falkmer, Sture
Magnusson, Karl-Eric
Borch, Kurt
Larsson, Marie
author_sort Tjomsland, Vegard
collection PubMed
description BACKGROUND: Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most common pancreatic cancer, is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence. METHODS: We examined the systemic influence ductal pancreatic adenocarcinoma (PDAC) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors, chronic pancreatitis, and age-matched controls. RESULTS: All groups examined, including PDAC, had decreased levels of myeloid DCs (MDC) and plasmacytoid DCs (PDC) and enhanced apoptosis in these cells as compared to controls. We found elevated levels of PGE2 and CXCL8 in subjects with PDAC, and chronic pancreatitis. Levels of these inflammatory factors were in part restored in PDAC after tumor resection, whereas the levels of DCs were impaired in the majority of these patients ~12 weeks after tumor removal. Our results prove that solid pancreatic tumors, including PDAC, systemically affect blood DCs. The impairments do not seem to be tumor-specific, since similar results were obtained in subjects with chronic pancreatitis. Furthermore, we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival. CONCLUSIONS: Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs. Furthermore, the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival.
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spelling pubmed-28475472010-03-31 Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity? Tjomsland, Vegard Sandström, Per Spångeus, Anna Messmer, Davorka Emilsson, Johan Falkmer, Ursula Falkmer, Sture Magnusson, Karl-Eric Borch, Kurt Larsson, Marie BMC Cancer Research Article BACKGROUND: Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most common pancreatic cancer, is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence. METHODS: We examined the systemic influence ductal pancreatic adenocarcinoma (PDAC) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors, chronic pancreatitis, and age-matched controls. RESULTS: All groups examined, including PDAC, had decreased levels of myeloid DCs (MDC) and plasmacytoid DCs (PDC) and enhanced apoptosis in these cells as compared to controls. We found elevated levels of PGE2 and CXCL8 in subjects with PDAC, and chronic pancreatitis. Levels of these inflammatory factors were in part restored in PDAC after tumor resection, whereas the levels of DCs were impaired in the majority of these patients ~12 weeks after tumor removal. Our results prove that solid pancreatic tumors, including PDAC, systemically affect blood DCs. The impairments do not seem to be tumor-specific, since similar results were obtained in subjects with chronic pancreatitis. Furthermore, we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival. CONCLUSIONS: Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs. Furthermore, the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival. BioMed Central 2010-03-09 /pmc/articles/PMC2847547/ /pubmed/20214814 http://dx.doi.org/10.1186/1471-2407-10-87 Text en Copyright ©2010 Tjomsland et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tjomsland, Vegard
Sandström, Per
Spångeus, Anna
Messmer, Davorka
Emilsson, Johan
Falkmer, Ursula
Falkmer, Sture
Magnusson, Karl-Eric
Borch, Kurt
Larsson, Marie
Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
title Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
title_full Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
title_fullStr Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
title_full_unstemmed Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
title_short Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
title_sort pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847547/
https://www.ncbi.nlm.nih.gov/pubmed/20214814
http://dx.doi.org/10.1186/1471-2407-10-87
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