RGD Reference Report - Semi mature blood dendritic cells exist in patients with ductal pancreatic adenocarcinoma owing to inflammatory factors released from the tumor. - Rat Genome Database

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Semi mature blood dendritic cells exist in patients with ductal pancreatic adenocarcinoma owing to inflammatory factors released from the tumor.

Authors: Tjomsland, V  Spangeus, A  Sandstrom, P  Borch, K  Messmer, D  Larsson, M 
Citation: Tjomsland V, etal., PLoS One. 2010 Oct 15;5(10):e13441.
RGD ID: 5490524
Pubmed: PMID:20976171   (View Abstract at PubMed)
PMCID: PMC2955544   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0013441   (Journal Full-text)

BACKGROUND: Much evidence exists regarding the fact that blood DCs, both myeloid DCs (MDCs) and plasmacytoid DCs (PDCs), are negatively affected in different types of cancer, with both reduced numbers and impaired functionality. Functional impairment of DCs in patients with pancreatic ductal adenocarcinoma (PDAC), may contribute to the poor clinical outcome. The aim of this study was to examine the effects PDAC had on blood DCs and elucidate the underlying mechanism responsible for the DC impairment. METHODOLOGY/PRINCIPAL FINDINGS: We examined the systemic influence PDAC exerted on blood DCs by ex vivo measuring numerous activation and maturation markers expressed on these cells. Furthermore, the effect patient plasma and the inflammatory factors CXCL8 and PGE(2) had on purified MDCs and PDCs from healthy donors was assessed and compared to the DCs existing in PDAC patients. We found a partial maturation of the blood MDCs and PDCs in PDAC patients with significantly enhanced expression of CD83, CD40, B7H3, PDL-1, CCR6, and CCR7 and decreased expression of ICOSL, and DCIR. These changes lead to impairment in their immunostimulatory function. Furthermore, chronic pancreatitis gave rise to DCs with similar semi-mature phenotype as seen in PDAC. Low expression of ICOSL was associated with poor prognosis. We found that the mechanism underlying this semi-maturation of DCs was inflammatory factors existing in the PDAC patients' plasma. Of note, PGE(2), which is elevated PDAC patient plasma, was one contributing factor to the changes seen in MDCs and PDCs phenotype. CONCLUSION/SIGNIFICANCE: Our findings point to a role for the systemic inflammation in transforming blood MDCs and PDCs into semi-mature cells in PDAC patients and we show a correlation between maturation status and clinical outcome. Thus, means to preserve a functional blood DC compartment in PDAC patients by diminishing the inflammation could facilitate their ability to control the disease and improve survival.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pancreatic ductal carcinoma  IEP 5490524protein:increased expression:dendritic cellRGD 
pancreatic ductal carcinoma  ISOCD40 (Homo sapiens)5490524; 5490524protein:increased expression:dendritic cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd40  (CD40 molecule)

Genes (Mus musculus)
Cd40  (CD40 antigen)

Genes (Homo sapiens)
CD40  (CD40 molecule)


Additional Information