Th1 and Th2 Profiles in Patients With Pancreatic Cancer Compared With Chronic Pancreatitis

Seicean, Andrada; Popa, Daniela; Mocan, Teodora; Cristea,; Berindan‐Neagoe, Ioana

doi:10.1097/mpa.0b013e31819313d0

Cited by 12 publications

(16 citation statements)

References 7 publications

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“…Among other functions, it stimulates B cell growth and increases immunoglobulin secretion. Increased serum levels of IL5 have been found in patients with pancreatic adenocarcinoma compared to chronic pancreatitis, and this finding supports a systemic Th2 response in patients with pancreas cancer (11). However, the absolute levels of IL5 expressed in this study were too low to be clinically relevant, and many of the samples, both high and low risk, contained concentrations below the detectable limits of our assay.…”

Section: Discussionmentioning

confidence: 57%

“…Cell-mediated and humoral immune responses occur through Th1 and Th2 CD4+ T lymphocytes and their activity can be measured through quantification of the cytokines IL1, IL2, IL4, IL5, IL8, IL10, IL12, IL13, IFN-γ, and TNF-α (11). IL 1b is a key mediator of the inflammatory response, and is central to cell proliferation, differentiation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, cytokine markers of the Th1 and Th2 immune response have been shown to discriminate pancreatic cancer from chronic pancreatitis or normal pancreatic tissue in both serum and pancreatic juice samples (10-11). We hypothesized that dysplasia in IPMN invokes an immunogenic/proinflammatory microenvironment that could be quantified in the cyst fluid, and allow for the identification of high-grade dysplasia or carcinoma prior to operation.…”

Section: Introductionmentioning

confidence: 99%

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Cyst Fluid Interleukin-1β (IL1β) Levels Predict the Risk of Carcinoma in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Maker

Katabi

et al. 2011

Clinical Cancer Research

128

102

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Purpose: Biomarkers for high-grade dysplasia in patients with radiographically identified intraductal papillary mucinous neoplasms (IPMN) have not been described. We hypothesized that dysplasia in IPMN invokes an immunogenic/proinflammatory microenvironment that can be identified by cyst fluid cytokine levels.Experimental Design: Pancreatic cyst fluid aspirates were collected at resection (2005)(2006)(2007)(2008)(2009). Samples were grouped into low-risk [low-grade (n ¼ 6) or moderate dysplasia (n ¼ 15)] and high-risk groups [highgrade dysplasia (n ¼ 13) or carcinoma (n ¼ 6)]. Cytokine expression was determined using a multiplex sandwich immunoassay. Differences in cytokine expression were evaluated using the 2-sample t test. Sample classification was performed using a logistic regression adjusting for sample covariates.Results: IL5 and IL8 concentrations were higher in the cyst fluid from patients in the high-risk group than the low-risk group. Interleukin (IL)-1b concentrations were also higher in the cyst fluid from patients with high-grade dysplasia or cancer (n ¼ 19) than those with low-or moderate-grade dysplasia (n ¼ 21, 539 AE 255 pg/mL vs. 0.2 AE 0

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cyst Fluid Interleukin-1β (IL1β) Levels Predict the Risk of Carcinoma in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Maker

Katabi

et al. 2011

Clinical Cancer Research

128

102

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“…This protein modulates the proliferation and apoptosis of effector T cells, blocks T‐cell activation, induces T‐cell death, retains T cells in an anergic state within the tumor, and skews the cytokine secretion balance toward a T helper type 2 (Th2) immune response 15. Meanwhile, the presence of tumor infiltrating lymphocytes with high Th2/Th1 ratios is indicative of a poor prognosis in PDAC 109. Therefore, the activated PSCs surrounding cancer cells may inhibit T cell activity and maintain a unique tumor immunosuppressive microenvironment, thereby protecting the tumor from the host immune system (Fig.…”

Section: Roles Of Psc In the Invasion And Metastasis Of Pdacmentioning

confidence: 99%

Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma

Tang

Wang

Zhou

et al. 2012

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors with poor prognosis due to extremely high malignancy, low rate of eligibility for surgical resection and chemoradiation resistance. Increasing evidence indicate that the interaction between activated pancreatic stellate cells (PSCs) and PDAC cells plays an important role in the development of PDAC. By producing high levels of cytokines, chemotactic factors, growth factors and excessive extracellular matrix (ECM), PSCs create desmoplasia and a hypoxic microenvironment that promote the initiation, development, evasion of immune surveillance, invasion, metastasis and resistance to chemoradiation of PDAC. Therefore, targeting the interaction between PSCs and PDAC cells may represent a novel therapeutic approach to advanced PDAC, especially therapies that target PSCs of the pancreatic tumor microenvironment.Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal malignant tumors in humans with very poor prognosis, due to a variety of causes including the insidious onset, absence of efficient screening methods for early detection, low rate of surgical resection at the time of clinical presentation and chemoradiation resistance. 1 Although scholars have been committed during the last three decades to studying genetic and/or epigenetic molecular changes of PDAC cells and chemotherapy with a combination of cytotoxic drugs have been implemented, the survival of patients with PDAC has not yet significantly improved.2,3 Until recently, an encouraging FOLFIRINOX scheme was reported to provide a statistically and clinically significant benefit over single-agent gemcitabine in patients with advanced PDAC but Key words: pancreatic ductal adenocarcinoma, pancreatic stellate cells, tumor microenvironment Abbreviations: ADMR: adrenomedullin receptor; AM: adrenomedullin; ATRA: all-trans retinoic acid; CTGF: connective tissue growth factor; DCs: dendritic cells; ECM: extracellular matrix; EGF: epidermal growth factor; EMMPRIN: extracellular matrix metalloproteinase inducer; EMT: epithelial-mesenchymal transition; ET-1: endothelin-1; FGF: fibroblast-growth-factor; GFAP: glial-fibrillary-acidic protein; HGF: hepatocyte growth factor; HPDE: human pancreatic duct epithelial; HSCs: hepatic stellate cells; HUVEC: endothelial cells; IGF-1: insulin-like growth factor-1; IL: interleukin; MMPs: matrix metalloproteinases; NADPH: nicotinamide adenine dinucleotide phosphate; NO: nitric oxide; PAEE: palmitic acid ethyl ester; PCLMs: pancreatic cancer liver metastases; PDAC: pancreatic ductal adenocarcinoma; PDGF: platelet-derived growth factor; PEDF: pigment epithelium-derived factor; PK: prokineticin; PKR: prokineticin receptor; PSCs: pancreatic stellate cells; ROS: oxygen species; Runx-2: Runt-related transcription factor-2; SDF-1: stromal cell-derived factor-1; sFRP4: secreted frizzled-related protein 4; SMO: smoothened; a-SMA: a-smooth muscle actin; SPARC: secreted protein acidic and rich in cysteine; TFF1: trefoil factor 1; TGF-b: transforming gr...

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“…56 Cytokine markers of a Th1 and Th2 immune response have been shown to discriminate pancreatic cancer from chronic pancreatitis or normal pancreatic tissue in both serum and pancreatic juice samples. 57, 58 Inflammation in pancreatic IPMN may lead to severe dysplasia and be reflected in inflammatory mediators that can be measured in the cyst fluid. Alternatively, increasing levels of cyst dysplasia may initiate an immune response that can be quantified by evaluation of cyst fluid cytokines.…”

Section: Introductionmentioning

confidence: 99%

Cyst Fluid Biomarkers for Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Critical Review from the International Expert Meeting on Pancreatic Branch-Duct-Intraductal Papillary Mucinous Neoplasms

Maker

Carrara

Jamieson

et al. 2015

Journal of the American College of Surgeons

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Th1 and Th2 Profiles in Patients With Pancreatic Cancer Compared With Chronic Pancreatitis

Cited by 12 publications

References 7 publications

Cyst Fluid Interleukin-1β (IL1β) Levels Predict the Risk of Carcinoma in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Cyst Fluid Interleukin-1β (IL1β) Levels Predict the Risk of Carcinoma in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma

Cyst Fluid Biomarkers for Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Critical Review from the International Expert Meeting on Pancreatic Branch-Duct-Intraductal Papillary Mucinous Neoplasms

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